MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Trends in Biochemical Sciences' source. Sun, 21 Mar 2010 16:58:23 +0100 http://www.medworm.com/index.php?rid=3385872&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20299225%26dopt%3DAbstract Authors: Taatjes DJ The Mediator complex interacts extensively with the RNA polymerase II enzyme and regulates its ability to express protein-coding genes. The mechanisms by which Mediator regulates gene expression remain poorly understood, in part because the structure of Mediator and even its composition can change, depending upon the promoter context. Combined with the sheer size of the human Mediator complex (26 subunits, 1.2 MDa), this structural adaptability bestows seemingly unlimited regulatory potential within the complex. Recent efforts to understand Mediator structure and function have identified expanded roles that include control of both pre- and post-initiation events; it is also evident that Mediator performs both general and gene-specific roles to regulate gene expressi... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3385872 Tue, 16 Mar 2010 00:00:00 +0100 3385872 http://www.medworm.com/index.php?rid=3385873&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20236825%26dopt%3DAbstract Authors: Dezwaan DC, Freeman BC The telomere environment requires an efficient means to assemble and disassemble a multitude of structures to operate correctly and to help achieve cellular homeostasis. Telomeres are challenged by a common binding specificity displayed by many of the protein components for telomeric DNA, which could result in competitive DNA interactions, and by a cell cycle-restricted timing of events, which enforces a narrow working period in which to perform numerous tasks. In this review, we discuss how the HSP90 molecular chaperone network avoids these obstacles and facilitates an effective operation of the telomere system. PMID: 20236825 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3385873 Mon, 15 Mar 2010 00:00:00 +0100 3385873 http://www.medworm.com/index.php?rid=3339934&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20202851%26dopt%3DAbstract Authors: Beddoe T, Paton AW, Le Nours J, Rossjohn J, Paton JC AB(5) toxins are important virulence factors for several major bacterial pathogens, including Bordetella pertussis, Vibrio cholerae, Shigella dysenteriae and at least two distinct pathotypes of Escherichia coli. The AB(5) toxins are so named because they comprise a catalytic A-subunit, which is responsible for disruption of essential host functions, and a pentameric B-subunit that binds to specific glycan receptors on the target cell surface. The molecular mechanisms by which the AB(5) toxins cause disease have been largely unravelled, including recent insights into a novel AB(5) toxin family, subtilase cytotoxin (SubAB). Furthermore, AB(5) toxins have become a valuable tool for studying fundamental cellular functions, and a... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3339934 Tue, 02 Mar 2010 00:00:00 +0100 3339934 http://www.medworm.com/index.php?rid=3327991&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20194025%26dopt%3DAbstract Authors: Svejstrup JQ Maintaining genome integrity is crucial for correctly regulated gene expression. Conversely, the process of transcription fundamentally impinges on genome stability, necessitating cellular mechanisms that lessen the genome destabilizing effect of reading genes. This review provides an overview of our present knowledge of how eukaryotic RNA polymerase II transcription affects, and is affected by, other DNA-related processes such as chromatin remodeling, DNA repair, recombination and replication. PMID: 20194025 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3327991 Sat, 27 Feb 2010 00:00:00 +0100 3327991 http://www.medworm.com/index.php?rid=3327992&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20189811%26dopt%3DAbstract Authors: Luhtala N, Parker R Ribonucleases of the T2 family are found in the genomes of protozoans, plants, bacteria, animals and viruses. A broad range of biological roles for these ribonucleases have been suggested, including scavenging of nucleic acids, degradation of self-RNA, serving as extra- or intracellular cytotoxins, and modulating host immune responses. Recently, RNaseT2 family members have been implicated in human pathologies such as cancer and parasitic diseases. Interestingly, certain functions of RNaseT2 family members are independent of their nuclease activity, suggesting that these proteins have additional functions. Moreover, humans lacking RNASET2 manifest a defect in neurological development, perhaps due to aberrant control of the immune system. We review the basic ... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3327992 Fri, 26 Feb 2010 00:00:00 +0100 3327992 http://www.medworm.com/index.php?rid=3327993&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20188572%26dopt%3DAbstract Authors: von Lintig J, Kiser PD, Golczak M, Palczewski K Recently, much progress has been made in elucidating the chemistry and metabolism of retinoids and carotenoids, as well as the structures of processing proteins related to vision. Carotenoids and their retinoid metabolites are isoprenoids, so only a limited number of chemical transformations are possible, and just a few of these occur naturally. Although there is an intriguing evolutionary conservation of the key components involved in the production and recycling of chromophores, these genes have also adapted to the specific requirements of insect and vertebrate vision. These 'ancestral footprints' in animal genomes bear witness to the common origin of the chemistry of vision, and will further stimulate research across evolution... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3327993 Wed, 24 Feb 2010 00:00:00 +0100 3327993 http://www.medworm.com/index.php?rid=3318931&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20181483%26dopt%3DAbstract Authors: Liu F, Walters KJ Ubiquitylation - the post-translational modification of proteins with ubiquitin - serves powerful regulatory roles in eukaryotes. It can label proteins for destruction or activate gene transcription. Despite its versatility, ubiquitin is used to signal for cellular events with exquisite specificity. To achieve both versatility and specificity, ubiquitin signaling pathways use multivalency, namely the coordinated use of multiple interaction surfaces. Multivalent interactions regulate each stage of ubiquitin signaling pathways, and appear within the ubiquitin signal, the ubiquitylated substrate, ubiquitin processing enzymes and ubiquitin recognition proteins. PMID: 20181483 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3318931 Mon, 22 Feb 2010 00:00:00 +0100 3318931 http://www.medworm.com/index.php?rid=3302811&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176488%26dopt%3DAbstract Authors: Tora L, Marc Timmers HT Early work established the TATA box as the predominant DNA element of core promoters which directed accurate transcription initiation by RNA polymerase II. This element is recognized by TATA-binding protein (TBP), the central DNA-binding subunit of TFIID. In vitro binding and structural experiments indicate that TBP has a strong preference for TATA and induces severe DNA bending. Recent in vivo studies in Saccharomyces cerevisiae indicate that TBP turnover is higher at TATA-containing than at TATA-less promoters; this turnover seems to be regulated by NC2 and Mot1p. We propose that bending of TATA by TBP acts in synergy with NC2 and Mot1p to release TBP more rapidly from TATA promoters in vivo, thus providing a rationale for the predominance of TATA box... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3302811 Sat, 20 Feb 2010 00:00:00 +0100 3302811 http://www.medworm.com/index.php?rid=3302813&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20172732%26dopt%3DAbstract This article focuses on the increasing importance of effective communication between scientists and their clinical colleagues. Some recent and innovative programs to facilitate these interactions are also discussed. PMID: 20172732 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3302813 Fri, 19 Feb 2010 00:00:00 +0100 3302813 http://www.medworm.com/index.php?rid=3302812&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20172733%26dopt%3DAbstract Authors: Wilson DM, Seidman MM DNA interstrand crosslinks (ICLs) can arise from reactions with endogenous chemicals, such as malondialdehyde - a lipid peroxidation product - or from exposure to various clinical anti-cancer drugs, most notably bifunctional alkylators and platinum compounds. Because they covalently link the two strands of DNA, ICLs completely block transcription and replication, and, as a result, are lethal to the cell. It is well established that proteins that function in nucleotide excision repair and homologous recombination are involved in ICL resolution. Recent work, coupled with a much earlier report, now suggest an emerging link between proteins of the base excision repair pathway and crosslink processing. PMID: 20172733 [PubMed - as supplied by publisher] (So... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3302812 Fri, 19 Feb 2010 00:00:00 +0100 3302812 http://www.medworm.com/index.php?rid=3291278&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20163964%26dopt%3DAbstract Authors: Johansson E, Macneill SA Three multi-subunit DNA polymerase enzymes lie at the heart of the chromosome replication machinery in the eukaryotic cell nucleus. Through a combination of genetic, molecular biological and biochemical analysis, significant advances have been made in understanding the essential roles played by each of these enzymes at the replication fork. Until very recently, however, little information was available on their three-dimensional structures. Lately, a series of crystallographic and electron microscopic studies has been published, allowing the structures of the complexes and their constituent subunits to be visualised in detail for the first time. Taken together, these studies provide significant insights into the molecular makeup of the replication mach... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3291278 Mon, 15 Feb 2010 00:00:00 +0100 3291278 http://www.medworm.com/index.php?rid=3254899&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20138767%26dopt%3DAbstract Authors: Hangen E, Blomgren K, Bénit P, Kroemer G, Modjtahedi N Apoptosis-inducing factor (AIF) was initially discovered as a caspase-independent death effector. AIF fulfills its lethal function after its release from mitochondria and its translocation to the nucleus of the dying cell. The contribution of AIF to programmed cell death is dependent upon the cell type and apoptotic insult. Recent in vivo data indicate that, in addition to its lethal activity, AIF plays a vital mitochondrial role in healthy cells. A segment of AIF which is dispensable for its apoptotic function carries an NADH-oxidase domain that regulates the respiratory chain complex I and is required for cell survival, proliferation and mitochondrial integrity. Mice that express reduced levels of AIF constitute a r... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3254899 Fri, 05 Feb 2010 00:00:00 +0100 3254899 http://www.medworm.com/index.php?rid=3254900&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20137954%26dopt%3DAbstract Authors: Panse VG, Johnson AW In eukaryotic cells, ribosomes are pre-assembled in the nucleus and exported to the cytoplasm where they undergo final maturation. This involves the release of trans-acting shuttling factors, transport factors, incorporation of the remaining ribosomal proteins, and final rRNA processing steps. Recent work, particularly on the large (60S) ribosomal subunit, has confirmed that the 60S subunit is exported from the nucleus in a functionally inactive state. Its arrival in the cytoplasm triggers events that render it translationally competent. Here we focus on these cytoplasmic maturation events and speculate why eukaryotic cells have evolved such an elaborate maturation pathway. PMID: 20137954 [PubMed - as supplied by publisher] (Source: Trends in Biochemic... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3254900 Wed, 03 Feb 2010 00:00:00 +0100 3254900 http://www.medworm.com/index.php?rid=3236594&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20116259%26dopt%3DAbstract Authors: Lundin VF, Leroux MR, Stirling PC Actins and tubulins are abundant cytoskeletal proteins that support diverse cellular processes. Owing to the unique properties of these filament-forming proteins, an intricate cellular machinery consisting minimally of the chaperonin CCT, prefoldin, phosducin-like proteins, and tubulin cofactors has evolved to facilitate their biogenesis. More recent evidence also suggests that regulated degradation pathways exist for actin (via TRIM32) and tubulin (via parkin or cofactor E-like). Collectively, these pathways maintain the quality control of cytoskeletal proteins ('proteostasis'), ensuring the appropriate function of microfilaments and microtubules. Here, we focus on the molecular mechanisms of the quality control of actin and tubulin, and disc... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3236594 Wed, 27 Jan 2010 00:00:00 +0100 3236594 http://www.medworm.com/index.php?rid=3218550&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20106667%26dopt%3DAbstract Authors: Hottiger MO, Hassa PO, Lüscher B, Schüler H, Koch-Nolte F ADP-ribosylation is a post-translational modification of proteins catalyzed by ADP-ribosyltransferases. It comprises the transfer of the ADP-ribose moiety from NAD(+) to specific amino acid residues on substrate proteins or to ADP-ribose itself. Currently, 22 human genes encoding proteins that possess an ADP-ribosyltransferase catalytic domain are known. Recent structural and enzymological evidence of poly(ADP-ribose)polymerase (PARP) family members demonstrate that earlier proposed names and classifications of these proteins are no longer accurate. Here we summarize these new findings and propose a new consensus nomenclature for all ADP-ribosyltransferases (ARTs) based on the catalyzed reaction and on structu... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3218550 Mon, 25 Jan 2010 00:00:00 +0100 3218550 http://www.medworm.com/index.php?rid=3212675&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20097077%26dopt%3DAbstract Authors: Lafontaine DL Ribosome synthesis is a major metabolic activity that involves hundreds of individual reactions, each of which is error-prone. Ribosomal insults occur in cis (alteration in rRNA sequences) and in trans (failure to bind to, or loss of, an assembly factor or ribosomal protein). In addition, specific growth conditions, such as starvation, require that excess ribosomes are turned over efficiently. Recent work indicates that cells evolved multiple strategies to recognize specifically, and target for clearance, ribosomes that are structurally and/or functionally deficient, as well as in excess. This surveillance is active at every step of the ribosome synthesis pathway and on mature ribosomes, involves nearly entirely different mechanisms for the small and large subuni... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3212675 Thu, 21 Jan 2010 00:00:00 +0100 3212675 http://www.medworm.com/index.php?rid=3212676&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20096590%26dopt%3DAbstract Authors: Kadota Y, Shirasu K, Guerois R The NLR (nucleotide-binding domain and leucine-rich repeat containing) proteins provide pathogen-sensing systems that are conserved in both plants and animals. They can be activated directly or indirectly by pathogen-derived molecules through mechanisms that remain largely elusive. Studies in plants revealed that the molecular chaperone, HSP90, and its co-chaperones, SGT1 and RAR1, are major stabilizing factors for NLR proteins. More recent work indicates that SGT1 and HSP90 are also required for the function of NLR proteins in mammals, underscoring the evolutionary conservation of innate immune system regulatory mechanisms. Comparative analyses of plant and mammalian NLR proteins, together with recent insights provided by the structure of SGT1-H... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3212676 Wed, 20 Jan 2010 00:00:00 +0100 3212676 http://www.medworm.com/index.php?rid=3200950&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20093032%26dopt%3DAbstract Authors: Shneider AM Often, new discoveries are not made at the moment when all of the necessary techniques and background knowledge become available. Instead, they are delayed as a result of mental inertia unrecognized by the scientist and/or the scientific community. In this paper, I introduce and classify various types of mental inertia that are common in science, using examples from the field of biology. PMID: 20093032 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3200950 Tue, 19 Jan 2010 00:00:00 +0100 3200950 http://www.medworm.com/index.php?rid=3164211&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20060301%26dopt%3DAbstract Authors: Grüning NM, Lehrach H, Ralser M The metabolic network has a modular architecture, is robust to perturbations, and responds to biological stimuli and environmental conditions. Through monitoring by metabolite responsive macromolecules, metabolic pathways interact with the transcriptome and proteome. Whereas pathway interconnecting cofactors and substrates report on the overall state of the network, specialised intermediates measure the activity of individual functional units. Transitions in the network affect many of these regulatory metabolites, facilitating the parallel regulation of the timing and control of diverse biological processes. The metabolic network controls its own balance, chromatin structure and the biosynthesis of molecular cofactors; moreover, metabolic s... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3164211 Wed, 06 Jan 2010 00:00:00 +0100 3164211 http://www.medworm.com/index.php?rid=3164210&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20060302%26dopt%3DAbstract Authors: Ji HF, Zhang HY Structural information regarding normal prion protein (PrP(C)) and the scrapie isoform (PrP(Sc)) is of vital importance for elucidating the pathogenesis of prion diseases (PDs). Despite successful determination of the three-dimensional structures of PrP(C), the structural details of PrP(Sc) remain elusive. Nevertheless, accumulated evidence indicates that beta-sheets comprise the basic building blocks of PrP(Sc). Consensus has been reached about the beta-sheet constitution of the N-terminus of PrP, but the constitution of C-terminal beta-sheets is heavily debated. By evaluating the most recent observations regarding the dynamics and structures of PrP, we propose that helix 2 is more likely than helices 1 and 3 to participate in beta-sheet formation. This hypoth... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3164210 Wed, 06 Jan 2010 00:00:00 +0100 3164210 http://www.medworm.com/index.php?rid=3129930&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20036556%26dopt%3DAbstract Authors: Moloney A, Sattelle DB, Lomas DA, Crowther DC The power of fruit fly genetics is being deployed against some of the most intractable and economically significant problems in modern medicine, the neurodegenerative diseases. Fly models of Alzheimer's disease can be exposed to the rich diversity of biological techniques that are available to the community and are providing new insights into disease mechanisms, and assisting in the identification of novel targets for therapy. Similar approaches might also help us to interpret the results of genome-wide association studies of human neurodegenerative diseases by allowing us to triage gene "hits" according to whether a candidate risk factor gene has a modifying effect on the disease phenotypes in fly model systems. PMID: 20036556... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3129930 Thu, 24 Dec 2009 00:00:00 +0100 3129930 http://www.medworm.com/index.php?rid=3105386&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20006513%26dopt%3DAbstract Authors: Bolaños JP, Almeida A, Moncada S Following inhibition of mitochondrial respiration neurons die rapidly, whereas astrocytes utilize glycolytically-generated ATP to increase their mitochondrial membrane potential, thus becoming more resistant to pro-apoptotic stimuli. Neurons are unable to increase glycolysis due to the lack of activity of the glycolysis-promoting enzyme 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase, isoform 3 (PFKFB3). In neurons, PFKFB3 is degraded constantly via the E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C)- CDH1. Glucose metabolism in neurons is directed mainly to the pentose phosphate pathway, leading to regeneration of reduced glutathione. In addition to their relevance to brain physiology and pathophysiology, these obser... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3105386 Fri, 11 Dec 2009 00:00:00 +0100 3105386 http://www.medworm.com/index.php?rid=3105385&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20006514%26dopt%3DAbstract Authors: Azzu V, Brand MD Mitochondrial uncoupling proteins disengage substrate oxidation from ADP phosphorylation by dissipating the proton electrochemical gradient that is required for ATP synthesis. In doing this, the archetypal uncoupling protein, UCP1, mediates adaptive thermogenesis. By contrast, its paralogues UCP2 and UCP3 are not thought to mediate whole body thermogenesis in mammals. Instead, they have been implicated in a variety of physiological and pathological processes, including protection from oxidative stress, negative regulation of glucose sensing systems and the adaptation of fatty acid oxidation capacity to starving. Although much work has been devoted to how these proteins are activated, little is known of the mechanisms that reverse this activation. PMID: 200... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3105385 Fri, 11 Dec 2009 00:00:00 +0100 3105385 http://www.medworm.com/index.php?rid=3105387&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20005723%26dopt%3DAbstract Authors: Shampay J PMID: 20005723 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3105387 Thu, 10 Dec 2009 00:00:00 +0100 3105387 http://www.medworm.com/index.php?rid=3065092&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19962317%26dopt%3DAbstract Authors: Rodnina MV, Wintermeyer W The award of this year's Nobel Prize in Chemistry to Ada E. Yonath, Venkatraman Ramakrishnan and Thomas A. Steitz honors their breakthrough achievement in determining the atomic structure of the ribosome. PMID: 19962317 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3065092 Wed, 02 Dec 2009 00:00:00 +0100 3065092 http://www.medworm.com/index.php?rid=3061599&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19959365%26dopt%3DAbstract Authors: Warf MB, Berglund JA Pre-mRNA splicing involves removing non-coding introns from RNA transcripts. It is carried out by the spliceosome, along with other auxiliary factors. In general, research in splicing has focused on the sequences within the pre-mRNA, without considering the structures that these sequences might form. We propose that the role of RNA structure deserves more consideration when thinking about splicing mechanisms. RNA structures can inhibit or aid binding of spliceosomal components to the pre-mRNA, or can increase splicing efficiency by bringing important sequences into close proximity. Recent reports have identified proteins and small molecules that can regulate splicing by modulating RNA structures, thereby expanding our knowledge of the mechanisms used to re... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3061599 Tue, 01 Dec 2009 00:00:00 +0100 3061599 http://www.medworm.com/index.php?rid=3019345&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19926288%26dopt%3DAbstract Authors: Braun RJ, Büttner S, Ring J, Kroemer G, Madeo F Neurodegeneration is characterized by the disease-specific loss of neuronal activity, culminating in the irreversible destruction of neurons. Neuronal cell death can proceed via distinct subroutines such as apoptosis and necrosis, but the underlying molecular mechanisms remain poorly understood. Saccharomyces cerevisiae is an established model for programmed cell death, characterized by distinct cell death pathways conserved from yeast to mammals. Recently, yeast models for several major classes of neurodegeneration, namely alpha-synucleinopathies, polyglutamine disorders, beta-amyloid diseases, tauopathies, and TDP-43 proteinopathies, have been established. Heterologous expression of the human proteins implicated in these d... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3019345 Tue, 17 Nov 2009 00:00:00 +0100 3019345 http://www.medworm.com/index.php?rid=3019344&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19926289%26dopt%3DAbstract Authors: Hernández G, Altmann M, Lasko P Translation in eukaryotes is a complex process that is closely regulated, mainly at the initiation step. Both universal and lineage-specific mechanisms regulate translation initiation. Considerable progress in our understanding of the regulation of translation has been achieved, but how these regulatory mechanisms evolved remains poorly understood. New discoveries in different fields suggest that the mechanisms that regulate translation emerged at different times during the evolution of eukaryotes, and that some initially evolved independently of the translation apparatus and were later incorporated into it. Overall, the emerging view suggests that 'tinkering' (i.e. co-opting and assembling molecules and regulatory mechanisms from other cel... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3019344 Tue, 17 Nov 2009 00:00:00 +0100 3019344 http://www.medworm.com/index.php?rid=3019343&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19926290%26dopt%3DAbstract Authors: Zhou HX, McCammon JA Protein dynamics are essential for virtually all protein functions, certainly for gating mechanisms of ion channels and regulation of enzyme catalysis. Ion channels usually feature a gate in the channel pore that prevents ion permeation in the closed state. Some bifunctional enzymes with two distant active sites use a tunnel to transport intermediate products; a gate can help prevent premature leakage. Enzymes with a buried active site also require a tunnel for substrate entrance; a gate along the tunnel can contribute to selectivity. The gates in these different contexts show distinct characteristics in sequence, structure and dynamics, but they also have common features. In particular, aromatic residues often appear to serve as gates, probably because of... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3019343 Tue, 17 Nov 2009 00:00:00 +0100 3019343 http://www.medworm.com/index.php?rid=3019342&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19926291%26dopt%3DAbstract Authors: Bankaitis VA, Mousley CJ, Schaaf G Lipid signaling pathways define central mechanisms for cellular regulation. Productive lipid signaling requires an orchestrated coupling between lipid metabolism, lipid organization and the action of protein machines that execute appropriate downstream reactions. Using membrane trafficking control as primary context, we explore the idea that the Sec14-protein superfamily defines a set of modules engineered for the sensing of specific aspects of lipid metabolism and subsequent transduction of 'sensing' information to a phosphoinositide-driven 'execution phase'. In this manner, the Sec14 superfamily connects diverse territories of the lipid metabolome with phosphoinositide signaling in a productive 'crosstalk' between these two systems. Mechani... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3019342 Tue, 17 Nov 2009 00:00:00 +0100 3019342 http://www.medworm.com/index.php?rid=3000527&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19913432%26dopt%3DAbstract Authors: Senapati S, Das S, Batra SK Mucins are high molecular weight glycoproteins that are involved in regulating diverse cellular activities both in normal and pathological conditions. Mucin activity and localization is mediated by several molecular mechanisms, including discrete interactions with other proteins. An understanding of the biochemistry behind the known interactions between mucins and other proteins, coupled with an appreciation of their pathophysiological significance, can lend insight into the development of novel therapeutic agents. Indeed, a recent study demonstrated that a cell permeable inhibitor, PMIP, that disrupts the MUC1-EGFR interaction, is effective in killing breast cancer cells in vitro and in tumor models. PMID: 19913432 [PubMed - as supplied by publ... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=3000527 Wed, 11 Nov 2009 00:00:00 +0100 3000527 http://www.medworm.com/index.php?rid=2959823&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19884009%26dopt%3DAbstract Authors: Wu D, Pan W GSK3 is one of the few signaling mediators that play central roles in a diverse range of signaling pathways, including those activated by Wnts, hedgehog, growth factors, cytokines, and G protein-coupled ligands. Although the inhibition of GSK3-mediated beta-catenin phosphorylation is known to be the key event in Wnt-beta-catenin signaling, the mechanisms that underlie this event remain incompletely understood. The recent demonstration of GSK3 involvement in Wnt receptor phosphorylation illustrates the multifaceted roles that GSK3 plays in Wnt-beta-catenin signaling. In this review, we will summarize these recent results and offer explanations, hypotheses, and models to reconcile some of these observations. PMID: 19884009 [PubMed - as supplied by publisher] (Sou... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2959823 Sat, 31 Oct 2009 00:00:00 +0100 2959823 http://www.medworm.com/index.php?rid=2959824&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19879149%26dopt%3DAbstract Authors: Le Guezennec X, Bulavin DV The PP2C family serine/threonine phosphatase WIP1 is characterized by distinctive oncogenic properties mediated by inhibitory functions on several tumor suppressor pathways, including ATM, CHK2, p38MAPK and p53. PPM1D, the gene encoding WIP1, is aberrantly amplified in different types of human primary cancers, and its deletion in mice results in a profound tumor-resistant phenotype. Numerous downstream targets of WIP1 have been identified, and genetic studies confirm that some play a part in tumorigenesis. Recent evidence highlights a new role for WIP1 in the regulation of a cell-autonomous decline in proliferation of certain self-renewing cell types, including pancreatic beta-cells, with advancing age. These emerging functions of WIP1 make it a pote... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2959824 Wed, 28 Oct 2009 00:00:00 +0100 2959824 http://www.medworm.com/index.php?rid=2947830&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19875293%26dopt%3DAbstract Authors: Cybulski N, Hall MN Research on TOR has grown exponentially during the last decade, generating a complex model of the TOR signaling network. Rapamycin treatment provides a simple and straightforward method to inhibit the TOR signaling pathway and to study the influence of TOR on multiple cellular processes. The discovery of two distinct TOR complexes, TORC1 and TORC2, showed that studies using rapamycin targeted only one TOR signaling branch. TORC1 is directly inhibited by rapamycin, whereas TORC2 is not. There is no known TORC2-specific inhibitor, so genetic manipulation is required to study its biological function(s). Many studies in genetically tractable model organisms have expanded our understanding of TORC2 signaling. Here we focus on the TORC2 signaling pathway as revea... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2947830 Tue, 27 Oct 2009 00:00:00 +0100 2947830 http://www.medworm.com/index.php?rid=2947829&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19875294%26dopt%3DAbstract Authors: Huen MS, Chen J The remarkably coordinated nature of the DNA damage response pathway relies on numerous mechanisms that facilitate the assembly of checkpoint and repair factors at DNA breaks. Post-translational modifications on and around chromatin have critical roles in allowing the timely and sequential assembly of DNA damage responsive elements at the vicinity of DNA breaks. Notably, recent advances in forward genetics and proteomics-based approaches have enabled the identification of novel components within the DNA damage response pathway, providing a more comprehensive picture of the molecular network that assists in the detection and propagation of DNA damage signals. PMID: 19875294 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2947829 Tue, 27 Oct 2009 00:00:00 +0100 2947829 http://www.medworm.com/index.php?rid=2944176&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19864144%26dopt%3DAbstract Authors: Houslay MD It is becoming increasingly apparent that spatial regulation of cell signalling processes is critical to normal cellular function. In this regard, cAMP signalling regulates many pivotal cellular processes and has provided the paradigm for signal compartmentalization. Recent advances show that isoforms of the cAMP-degrading phosphodiesterase-4 (PDE4) family are targeted to discrete signalling complexes. There they sculpt local cAMP gradients that can be detected by genetically encoded cAMP sensors, and gate the activation of spatially localized signalling through sequestered PKA and EPAC sub-populations. Genes for these important regulatory enzymes are linked to schizophrenia, stroke and asthma, thus indicating the therapeutic potential that selective inhibitors coul... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2944176 Mon, 26 Oct 2009 00:00:00 +0100 2944176 http://www.medworm.com/index.php?rid=2935217&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19853458%26dopt%3DAbstract Authors: Aebi M, Bernasconi R, Clerc S, Molinari M The processing of N-linked glycans determines secretory protein homeostasis in the eukaryotic cell. Folding and degradation of glycoproteins in the endoplasmic reticulum (ER) are regulated by molecular chaperones and enzymes recruited by specific oligosaccharide structures. Recent findings have identified several components of this protein quality control system that specifically modify N-linked glycans, thereby generating oligosaccharide structures recognized by carbohydrate-binding proteins, lectins. In turn, lectins direct newly synthesized polypeptides to the folding, secretion or degradation pathways. The "glyco-code of the ER" displays the folding status of a multitude of cargo proteins. Deciphering this code will be instrumental... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2935217 Wed, 21 Oct 2009 00:00:00 +0100 2935217 http://www.medworm.com/index.php?rid=2923950&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19846312%26dopt%3DAbstract Authors: Lue NF Telomeres, the specialized nucleoprotein structures located at linear eukaryotic chromosomal termini, are essential for chromosome stability and are maintained by the special reverse transcriptase named telomerase. In the Saccharomycotina subphylum of budding yeast, telomere repeat sequences and binding factors, as well as telomerase components, are exceptionally diverse and distinct from those found in other eukaryotes. In this survey, I report a comparative analysis of the domain structures of telomere and telomerase-related factors made possible by the recent sequencing of multiple yeast genomes. This analysis revealed both conserved and variable aspects of telomere maintenance. Based on these findings, I propose a plausible series of evolutionary events in budding y... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2923950 Mon, 19 Oct 2009 00:00:00 +0100 2923950 http://www.medworm.com/index.php?rid=2923949&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19846313%26dopt%3DAbstract Authors: Mittermaier AK, Kay LE Biological macromolecules are highly flexible and continually undergo conformational fluctuations on a broad spectrum of timescales. It has long been recognized that dynamics have an important role in the action of these molecules. However, the relationship between molecular function and motion is extremely challenging to delineate, because the conformational space available to macromolecules is vast and the relevant excursions can be infrequent and short-lived. Recent advances in solution nuclear magnetic resonance (NMR) spectroscopy permit biomolecular dynamics to be observed with unprecedented detail. Applications of these new NMR techniques to the study of fundamental processes such as binding and catalysis have provided new insights into how living ... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2923949 Mon, 19 Oct 2009 00:00:00 +0100 2923949 http://www.medworm.com/index.php?rid=2909683&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19837592%26dopt%3DAbstract Authors: Tsai CJ, Ma B, Nussinov R How can a single hub protein bind so many different partners? Numerous studies have sought differences between hubs and non-hubs to explain what makes a protein a hub and how a shared hub-binding site can be promiscuous, yet at the same time be specific. Here, we suggest that the problem is largely non-existent and resides in the popular representation of protein interaction networks: protein products derived from a single gene, even if different, are clustered in maps into a single node. This leads to the impression that a single protein binds to a very large number of partners. In reality, it does not; rather, protein networks reflect the combination of multiple proteins, each with a distinct conformation. PMID: 19837592 [PubMed - as supplied by... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2909683 Thu, 15 Oct 2009 23:00:00 +0100 2909683 http://www.medworm.com/index.php?rid=2909687&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19836958%26dopt%3DAbstract Authors: Hofmann KP, Scheerer P, Hildebrand PW, Choe HW, Park JH, Heck M, Ernst OP G protein-coupled receptors (GPCRs) are ubiquitous signal transducers in cell membranes, as well as important drug targets. Interaction with extracellular agonists turns the seven transmembrane helix (7TM) scaffold of a GPCR into a catalyst for GDP and GTP exchange in heterotrimeric Galphabetagamma proteins. Activation of the model GPCR, rhodopsin, is triggered by photoisomerization of its retinal ligand. From the augmentation of biochemical and biophysical studies by recent high-resolution 3D structures, its activation intermediates can now be interpreted as the stepwise engagement of protein domains. Rearrangement of TM5-TM6 opens a crevice at the cytoplasmic side of the receptor into which the C termi... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2909687 Wed, 14 Oct 2009 23:00:00 +0100 2909687 http://www.medworm.com/index.php?rid=2909686&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19836959%26dopt%3DAbstract Authors: Zich J, Hardwick KG Due to the highly orchestrated stages of mitosis, cells segregate their chromosomes with incredibly high fidelity. One of the principal 'conductors' is the spindle checkpoint, which regulates mitotic progression. Specifically, it delays anaphase onset until all chromosomes are attached in a bi-oriented fashion to spindle microtubules. This delay stems from inhibition of Cdc20, an activator of an E3 ubiquitin ligase known as the anaphase-promoting complex or cyclosome (APC/C). Several recent advances in our mechanistic understanding of this important cell cycle control have been made. Although still poorly understood, signalling roles for checkpoint kinases and their opposing phosphatases continue to be uncovered, and the key substrates gradually identified.... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2909686 Wed, 14 Oct 2009 23:00:00 +0100 2909686 http://www.medworm.com/index.php?rid=2909685&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19836960%26dopt%3DAbstract Authors: Billur M, Bartunik HD, Singh PB A large body of work in various organisms has shown that the presence of HP1 structural proteins and methylated lysine 9 of histone H3 (H3K9me) represent the characteristic hallmarks of heterochromatin. We propose that a more critical assessment of the physiological importance of the H3K9me-HP1 interaction is warranted in light of recent studies on the mammalian HP1beta protein. Based on this new research, we conclude that the essential function of HP1beta (and perhaps that of its orthologues in other species) lies outside the canonical heterochromatic H3K9me-HP1 interaction. We suggest instead that binding of a small fraction of HP1beta to the H3 histone fold performs a critical role in heterochromatin function and organismal survival. PMID... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2909685 Wed, 14 Oct 2009 23:00:00 +0100 2909685 http://www.medworm.com/index.php?rid=2909684&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19836961%26dopt%3DAbstract Authors: Young MT P2X receptors are non-selective cation channels gated by extracellular ATP. They play key roles in various physiological processes such as nerve transmission, pain sensation and the response to inflammation, making them attractive drug targets for the treatment of inflammatory pain. The recent report of the three-dimensional (3D) crystal structure of zebrafish P2X4.1 represents a step change in our understanding of these membrane ion channels, where previously only low-resolution structural data and inferences from indirect structure-function studies were available. The purpose of this review is to place previous work within the context of the new 3D structure, and to summarize the key questions and challenges which await P2X researchers as we move into the post-struc... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2909684 Wed, 14 Oct 2009 23:00:00 +0100 2909684 http://www.medworm.com/index.php?rid=2902004&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19828319%26dopt%3DAbstract Authors: Mauxion F, Chen CY, Séraphin B, Shyu AB BTG/TOB factors are a family of antiproliferative proteins whose expression is altered in numerous cancers. They have been implicated in cell differentiation, development and apoptosis. Although proposed to affect transcriptional regulation, these factors interact with CAF1, a subunit of the main eukaryotic deadenylase, and with poly(A)-binding-proteins, strongly suggesting a role in post-transcriptional regulation of gene expression. The recent determination of the structures of BTG2, TOB1 N-terminal domain (TOB1N138) and TOB1N138-CAF1 complexes support a role for BTG/TOB proteins in mRNA deadenylation, a function corroborated by recently published functional characterizations. We highlight molecular mechanisms by which BTG/TOB pro... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2902004 Sun, 11 Oct 2009 23:00:00 +0100 2902004 http://www.medworm.com/index.php?rid=2887240&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19819701%26dopt%3DAbstract Authors: Gutmann DA, Ward A, Urbatsch IL, Chang G, van Veen HW Multidrug ABC transporters can transport a wide range of drugs from the cell. Ongoing studies of the prototype mammalian multidrug resistance ATP-binding cassette transporter P-glycoprotein (ABCB1) have revealed many intriguing functional and biochemical features. However, a gap remains in our knowledge regarding the molecular basis of its broad specificity for structurally unrelated ligands. Recently, the first crystal structures of ligand-free and ligand-bound ABCB1 showed ligand binding in a cavity between its two membrane domains, and earlier observations on polyspecificity can now be interpreted in a structural context. Comparison of the new ABCB1 crystal structures with structures of bacterial homologs suggests a crit... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2887240 Thu, 08 Oct 2009 23:00:00 +0100 2887240 http://www.medworm.com/index.php?rid=2887242&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19818633%26dopt%3DAbstract Authors: Birts CN, Barton CH, Wilton DC Group IIA phospholipase A2 (PLA2) is a low-molecular-mass secreted PLA2 enzyme that has been identified as an acute phase protein with a role in the inflammatory response to infection and trauma. The protein is possibly unique in being highly cationic and having a global distribution of surface arginine and lysine residues. This structure supports two functions of the protein. (1) An anti-bacterial role where the enzyme is targeted to the anionic cell membrane of Gram-positive bacteria and phospholipid hydrolysis assists in bacterial killing. (2) A proposed non-catalytic role in which the protein forms supramolecular aggregates with anionic phospholipid vesicles or debris. These aggregates are then internalized via interactions with cell surface ... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2887242 Wed, 07 Oct 2009 23:00:00 +0100 2887242 http://www.medworm.com/index.php?rid=2887241&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19819149%26dopt%3DAbstract Authors: Mellert HS, McMahon SB Protein phosphorylation is regulated dynamically in eukaryotic cells via modulation of the enzymatic activity of kinases and phosphatases. Like phosphorylation, acetylation has emerged as a critical regulatory protein modification that is altered dynamically in response to diverse cellular cues. Moreover, acetyltransferases and deacetylases are tightly linked to cellular signaling pathways. Recent studies provide clues about the mechanisms utilized to regulate acetyltransferases and deacetylases. The therapeutic value of deacetylase inhibitors suggests that understanding acetylation pathways will directly impact our ability to rationally target these enzymes in patients. Recently discovered mechanisms that directly regulate the catalytic activity of acet... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2887241 Wed, 07 Oct 2009 23:00:00 +0100 2887241 http://www.medworm.com/index.php?rid=2887245&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19818630%26dopt%3DAbstract Authors: Monie TP, Bryant CE, Gay NJ The Toll-like receptors and NOD-like receptors are key families in the innate immune response. The specific detection of activating ligand facilitates receptor interactions, the formation of multiprotein signalling complexes and initiation of signal transduction cascades. This process can trigger the upregulation of proinflammatory mediators, apoptosis, and modulation of other immune defences. Recently, significant advances have been made in the identification of new activating ligands and the determination of the molecular basis of ligand recognition within these receptor families. Understanding these processes provides information essential to the development of new vaccine adjuvants and the treatment of infectious diseases, inflammatory disorders... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2887245 Tue, 06 Oct 2009 23:00:00 +0100 2887245 http://www.medworm.com/index.php?rid=2887244&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19818631%26dopt%3DAbstract Authors: Gentry MS, Dixon JE, Worby CA Reversible phosphorylation modulates nearly every step of glycogenesis and glycogenolysis. Multiple metabolic disorders are the result of defective enzymes that control these phosphorylation events, enzymes that were identified biochemically before the advent of the molecular biology era. Lafora disease is a metabolic disorder resulting in accumulation of water-insoluble glucan in the cytoplasm, and manifests as a debilitating neurodegeneration that ends with the death of the patient. Unlike most metabolic disorders, the link between Lafora disease and metabolism has not been defined in almost 100 years. The results of recent studies with mammalian cells, mouse models, eukaryotic algae, and plants have begun to define the molecular mechanisms that... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2887244 Tue, 06 Oct 2009 23:00:00 +0100 2887244 http://www.medworm.com/index.php?rid=2887243&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19818632%26dopt%3DAbstract Authors: Jackson S, Xiong Y The evolutionarily conserved cullin family proteins can assemble as many as 400 distinct E3 ubiquitin ligase complexes that regulate diverse cellular pathways. CUL4, one of three founding cullins conserved from yeast to humans, uses a large beta-propeller protein, DDB1, as a linker to interact with a subset of WD40 proteins that serve as substrate receptors, forming as many as 90 E3 complexes in mammals. Many CRL4 complexes are involved in chromatin regulation and are frequently hijacked by different viruses. PMID: 19818632 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2887243 Tue, 06 Oct 2009 23:00:00 +0100 2887243 http://www.medworm.com/index.php?rid=2877143&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19811920%26dopt%3DAbstract Authors: Rouhier N, Couturier J, Johnson MK, Jacquot JP Glutaredoxins, proteins traditionally involved in redox reactions, are also required for iron-sulfur cluster assembly and haem biosynthesis. These new roles are probably related to the ability of some glutaredoxins to bind labile [2Fe-2S] clusters and to transfer them rapidly and efficiently to acceptor proteins. Recent results point to putative roles for glutaredoxins in the sensing of cellular iron and in iron-sulfur cluster biogenesis, either as scaffold proteins for the de novo synthesis of iron-sulfur clusters or as carrier proteins for the transfer of preformed iron-sulfur clusters. Based on prokaryote genome analysis and in vivo studies of iron regulation in yeast, we propose putative new roles and binding partners for glut... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2877143 Sun, 04 Oct 2009 23:00:00 +0100 2877143 http://www.medworm.com/index.php?rid=2863136&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19801192%26dopt%3DAbstract Authors: Fuentes G, Valencia A Components of signal transduction pathways have evolved as connected hubs, recognizing several binding partners with remarkable affinities and specificities. Ras is one of these hubs, sensitive to rapid and subtle changes, thus enabling the correct transfer of information. The dynamic nature of such systems makes their structural characterization challenging, despite the vast amount of experimental data available. These data, however, can be used as a restraint for generating comprehensive models of the association of Ras with its effectors. We believe that by following this type of approach, the derived 3D models can provide atomistic understanding of important biological issues, such as how Ras discriminates between the Ras binding domains of its variou... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2863136 Thu, 01 Oct 2009 23:00:00 +0100 2863136 http://www.medworm.com/index.php?rid=2858203&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19796953%26dopt%3DAbstract Authors: Brown J, Jones EY, Forbes BE Insulin-like growth factor-II (IGF-II) is a key regulator of cell growth, survival, migration and differentiation. Its pivotal role in these processes requires tight regulation of both expression and activity. The type 1 IGF receptor tyrosine kinase (IGF-1R) mediates IGF-II actions, and a family of six high affinity IGF binding proteins (IGFBPs) regulates IGF-II circulating half-life and its availability to bind IGF-1R. In addition, the type 2 IGF receptor (IGF2R; also called the cation-independent mannose-6-phosphate receptor) modulates the circulating and tissue levels of IGF-II by targeting it to lysosomes for degradation. The recently elucidated crystal structure of IGF-II-IGF2R complex provides new insight into IGF-II regulation, and reveals a... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2858203 Mon, 28 Sep 2009 23:00:00 +0100 2858203 http://www.medworm.com/index.php?rid=2858202&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19796954%26dopt%3DAbstract Authors: Skinner-Adams TS, Stack CM, Trenholme KR, Brown CL, Grembecka J, Lowther J, Mucha A, Drag M, Kafarski P, McGowan S, Whisstock JC, Gardiner DL, Dalton JP The neutral aminopeptidases M1 alanyl aminopeptidase (PfM1AAP) and M17 leucine aminopeptidase (PfM17LAP) of the human malaria parasite Plasmodium falciparum are targets for the development of novel anti-malarial drugs. Although the functions of these enzymes remain unknown, they are believed to act in the terminal stages of haemoglobin degradation, generating amino acids essential for parasite growth and development. Inhibitors of both enzymes are lethal to P. falciparum in culture and kill the murine malaria P. chabaudi in vivo. Recent biochemical, structural and functional studies provide the substrate specificity and mechan... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2858202 Mon, 28 Sep 2009 23:00:00 +0100 2858202 http://www.medworm.com/index.php?rid=2847063&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19786350%26dopt%3DAbstract Authors: Lievens S, Lemmens I, Tavernier J A diverse series of mammalian two-hybrid technologies for the detection of protein-protein interactions have emerged in the past few years, complementing the established yeast two-hybrid approach. Given the mammalian background in which they operate, these assays open new avenues to study the dynamics of mammalian protein interaction networks, i.e. the temporal, spatial and functional modulation of protein-protein associations. In addition, novel assay formats are available that enable high-throughput mammalian two-hybrid applications, facilitating their use in large-scale interactome mapping projects. Finally, as they can be applied in drug discovery and development programs, these techniques also offer exciting new opportunities for biomedic... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2847063 Fri, 25 Sep 2009 23:00:00 +0100 2847063 http://www.medworm.com/index.php?rid=2829061&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19773172%26dopt%3DAbstract Authors: Exley C If one was asked to produce a set of 'Trump Cards' based upon 'Forces of Nature Defining Life on Earth' then which card would be 'Top Trump'? I was recently chastised on the Darwin Today website for suggesting Darwin and 'natural selection' rather than, for example, Newton and 'gravity'. Although there is no denying the significance of gravity, my argument in favour of natural selection is simply that gravity is just one factor that contributes towards an outcome which ultimately is defined by natural selection. Both the beauty and the brilliance of natural selection are reflected in its omnipotence to explain the myriad observations of life and, as I will affirm herein, its explanation of the biological essentiality of aluminium and silicon is no exception. PMID: ... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2829061 Fri, 18 Sep 2009 23:00:00 +0100 2829061 http://www.medworm.com/index.php?rid=2797262&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19748784%26dopt%3DAbstract Authors: Jones PM, O'Mara ML, George AM ATP-binding cassette (ABC) transporters form one of the largest and most ancient of protein families. ABC transporters couple hydrolysis of ATP to vectorial translocation of diverse substrates across cellular membranes. Many human ABC transporters are medically important in causing, for example, multidrug resistance to cytotoxic drugs. Seven complete prokaryotic structures and one eukaryotic structure have been solved for transporters from 2002 to date, and a wealth of research is being conducted on and around these structures to resolve the mechanistic conundrum of how these transporters couple ATP hydrolysis in cytosolic domains to substrate translocation through the transmembrane pore. Many questions remained unanswered about this mechanism, d... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2797262 Thu, 10 Sep 2009 23:00:00 +0100 2797262 http://www.medworm.com/index.php?rid=2786926&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19744855%26dopt%3DAbstract Authors: Gibson TJ Do kinases cascade? How well is cell regulation understood? What are the best ways to model regulatory systems? Attempts to answer such questions can have bearings on the way in which research is conducted. Fortunately there are recurring themes in regulatory processes from many different cellular contexts, which might provide useful guidance. Three principles seem to be almost universal: regulatory interactions are cooperative; regulatory decisions are made by large dynamic protein complexes; and regulation is intricately networked. A fourth principle, although not universal, is remarkably common: regulatory proteins are actively placed where they are needed. Here, I argue that the true nature of cell signalling and our perceptions of it are in a state of discord. T... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2786926 Mon, 07 Sep 2009 23:00:00 +0100 2786926 http://www.medworm.com/index.php?rid=2786927&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19740663%26dopt%3DAbstract Authors: Mehra A, Baker CL, Loros JJ, Dunlap JC The pace has quickened in circadian biology research. In particular, an abundance of results focused on post-translational modifications (PTMs) is sharpening our view of circadian molecular clockworks. PTMs affect nearly all aspects of clock biology; in some cases they are essential for clock function and in others, they provide layers of regulatory fine-tuning. Our goal is to review recent advances in clock PTMs, help make sense of emerging themes, and spotlight intriguing (and perhaps controversial) new findings. We focus on PTMs affecting the core functions of eukaryotic clocks, in particular the functionally related oscillators in Neurospora crassa, Drosophila melanogaster, and mammalian cells. PMID: 19740663 [PubMed - as supplied... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2786927 Sun, 06 Sep 2009 23:00:00 +0100 2786927 http://www.medworm.com/index.php?rid=2775110&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19733480%26dopt%3DAbstract Authors: Kang J, Shakya A, Tantin D It is a classic story of two related transcription factors. Oct4 is a potent regulator of pluripotency during early mammalian embryonic development, and is notable for its ability to convert adult somatic cells to pluripotency. The widely expressed Oct1 protein shares significant homology with Oct4, binds to the same sequences, regulates common target genes, and shares common modes of upstream regulation, including the ability to respond to cellular stress. Both proteins are also associated with malignancy, yet Oct1 cannot substitute for Oct4 in the generation of pluripotency. The molecular underpinnings of these phenomena are emerging, as are the consequences for adult stem cells and cancer, and thereby hangs a tale. PMID: 19733480 [PubMed - as ... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2775110 Wed, 02 Sep 2009 23:00:00 +0100 2775110 http://www.medworm.com/index.php?rid=2775113&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19733081%26dopt%3DAbstract Authors: Eisenbach M PMID: 19733081 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2775113 Tue, 01 Sep 2009 23:00:00 +0100 2775113 http://www.medworm.com/index.php?rid=2775112&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19733082%26dopt%3DAbstract Authors: Markovic D, Grammatopoulos DK The family of G-protein coupled receptors (GPCRs) is one of the largest protein families in the mammalian genome with a fundamental role in cell biology. GPCR activity is finely tuned by various transcriptional, post-transcriptional and post-translational mechanisms. Alternative pre-mRNA splicing is now emerging as a crucial process regulating GPCR biological function. Intriguingly, this mechanism appears to extensively target the Secretin family of GPCRs, especially the exon that encodes a 14 amino acid sequence that forms the distal part of 7th transmembrane helix, and exhibits an unusually high level of sequence conservation among most Secretin GPCRs. Do the "TMD7-short" receptor variants have a role as novel regulators of GPCR signallng and, i... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2775112 Tue, 01 Sep 2009 23:00:00 +0100 2775112 http://www.medworm.com/index.php?rid=2775111&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19733083%26dopt%3DAbstract Authors: Fux L, Ilan N, Sanderson RD, Vlodavsky I Heparanase activity is strongly implicated in structural remodeling of the extracellular matrix, a process which can lead to invasion by tumor cells. In addition, heparanase augments signaling cascades leading to enhanced phosphorylation of selected protein kinases and increased gene transcription associated with aggressive tumor progression. This function is apparently independent of heparan sulfate and enzyme activity, and is mediated by a novel protein domain localized at the heparanase C-terminus. Moreover, the functional repertoire of heparanase is expanded by its regulation of syndecan clustering, shedding, and mitogen binding. Recent reports indicate that modified glycol-split heparin, which inhibits heparanase activity, can prof... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2775111 Tue, 01 Sep 2009 23:00:00 +0100 2775111 http://www.medworm.com/index.php?rid=2770448&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19729309%26dopt%3DAbstract Authors: Lago F, Gómez R, Gómez-Reino JJ, Dieguez C, Gualillo O In the mid-1990s, interest in adipose tissue - until then generally regarded as a mere energy reserve - was revived by the discovery of leptin. Since then numerous other cytokine-like hormones have been isolated from white adipose tissue. These adipokines have been investigated in relation to obesity, metabolic syndrome, insulin resistance and other pathological conditions and processes. In addition, it is now established that adipokines play a role in the maintenance of an inflammatory state in adipose tissue and in the development of obesity and comorbidities. The contributions of individual adipokines in the pathophysiological features of obesity have yet to be determined in full, but recent data highlight imp... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2770448 Mon, 31 Aug 2009 23:00:00 +0100 2770448 http://www.medworm.com/index.php?rid=2770447&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19729310%26dopt%3DAbstract Authors: Berthon J, Fujikane R, Forterre P In all organisms, DNA and protein are synthesized by dedicated, but unrelated, machineries that move along distinct templates with no apparent coordination. Therefore, connections between DNA replication and translation are a priori unexpected. However, recent findings support the existence of such connections throughout the three domains of life. In particular, we recently identified in archaeal genomes a conserved association between genes encoding DNA replication and ribosome-related proteins which all have eukaryotic homologs. We believe that this gene organization is biologically relevant and, moreover, that it suggests the existence of a mechanism coupling DNA replication and translation in Archaea and Eukarya. PMID: 19729310 [PubMed... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2770447 Mon, 31 Aug 2009 23:00:00 +0100 2770447 http://www.medworm.com/index.php?rid=2770446&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19729311%26dopt%3DAbstract Authors: Schoenberg DR, Maquat LE The 5'-cap structure that typifies all polymerase II-transcribed RNAs plays important roles in pre-mRNA processing and mRNA export, translation and quality control. Removal of the cap is a regulated process that is considered to be the first irreversible step in mRNA decay. An emerging view challenges this idea: mRNAs have been identified in mammalian cells that lack sequences from their 5' ends but nevertheless appear to be modified with a cap or cap-like structure. Furthermore, a cytoplasmic form of capping enzyme was recently identified that, together with a novel kinase, generates capped ends from cleaved RNAs. These and other findings provide evidence for re-capping and its possible functions. PMID: 19729311 [PubMed - as supplied by publisher]... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2770446 Mon, 31 Aug 2009 23:00:00 +0100 2770446 http://www.medworm.com/index.php?rid=2766832&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19726197%26dopt%3DAbstract Authors: Ovaere P, Lippens S, Vandenabeele P, Declercq W It has become clear in recent years that serine proteases have an important role in epidermal homeostasis, and the signaling cascades are gradually being identified. For example, matriptase, prostasin and furin are implicated in a cascade that could activate ENaC, leading to epidermal barrier formation and hydration, probably in part through their involvement in filaggrin processing. Kallikreins can form a signaling cascade to coordinate corneocyte desquamation. Knowledge is also emerging about how endogenous inhibitors, calcium and pH control these cascades. It is becoming clear that some skin pathologies are associated with deregulated serine protease activity. Therefore, a deeper knowledge of the regulation of these serine pro... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2766832 Sun, 30 Aug 2009 23:00:00 +0100 2766832 http://www.medworm.com/index.php?rid=2766831&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19726198%26dopt%3DAbstract Authors: Privalov PL, Dragan AI, Crane-Robinson C Experimental data on protein-DNA interactions highlight a surprising peculiarity of protein binding to the minor groove: in contrast to major groove binding, which proceeds with heat release and does not induce substantial deformation of DNA, minor groove binding takes place at AT-rich sites, proceeds with heat absorption and results in significant DNA bending. By forming a highly ordered and dense spine in the minor groove of AT-rich DNA, water plays an essential role in defining the energetic signature of protein-minor groove binding. Removal of this water requires minimal work and results in significant loss of rigidity in the DNA, which can then easily acquire the conformation imposed by the bound protein. Therefore the introduction... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2766831 Sun, 30 Aug 2009 23:00:00 +0100 2766831 http://www.medworm.com/index.php?rid=2668323&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19647433%26dopt%3DAbstract Authors: de Groot NS, Sabate R, Ventura S Protein misfolding and aggregation into amyloid structures are associated with dozens of human diseases. Recent studies have provided compelling evidence for the existence of highly ordered, amyloid-like conformations in the insoluble inclusion bodies produced during heterologous protein expression in bacteria. Thus, amyloid aggregation seems to be an omnipresent process in both eukaryotic and prokaryotic organisms. Amyloid formation inside cell factories raises important safety concerns with regard to the toxicity and infectivity of recombinant proteins. Yet such findings also suggest that prokaryotic cells could be useful systems for studying how and why proteins aggregate in vivo, and they could also provide a biologically relevant backgroun... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2668323 Wed, 29 Jul 2009 23:00:00 +0100 2668323 http://www.medworm.com/index.php?rid=2668322&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19647434%26dopt%3DAbstract Authors: Munro JB, Sanbonmatsu KY, Spahn CM, Blanchard SC The molecular mechanisms by which tRNA molecules enter and transit the ribosome during mRNA translation remains elusive. However, recent genetic, biochemical and structural studies offer important new findings into the ordered sequence of events underpinning the translocation process that help place the molecular mechanism within reach. In particular, new structural and kinetic insights have been obtained regarding tRNA movements through 'hybrid state' configurations. These dynamic views reveal that the macromolecular ribosome particle, like many smaller proteins, has an intrinsic capacity to reversibly sample an ensemble of similarly stable native states. Such perspectives suggest that substrates, factors and environmental cues... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2668322 Wed, 29 Jul 2009 23:00:00 +0100 2668322 http://www.medworm.com/index.php?rid=2668321&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19647435%26dopt%3DAbstract Authors: Giglione C, Fieulaine S, Meinnel T Recent major advances have been made in understanding how cotranslational events are achieved in the course of protein biosynthesis. Specifically, several studies have shed light into the dynamic process of how nascent chains emerging from the ribosome are supported by protein biogenesis factors to ensure both processing and folding mechanisms. To take into account the awareness that coordination is needed, a new 'concerted model' recently proposed simultaneous action of both processes on the ribosome. In the model, any emerging nascent chain is first encountered by the chaperone trigger factor (TF), which forms an open cradle underneath the ribosomal exit tunnel. This cradle serves as a passive router that channels the nascent chains to the ... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2668321 Wed, 29 Jul 2009 23:00:00 +0100 2668321 http://www.medworm.com/index.php?rid=2668320&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19647436%26dopt%3DAbstract Authors: Gribaldo S, Talla E, Brochier-Armanet C Understanding the origin and evolution of haem copper dioxygen reductases (HCO O(2)Red), the terminal enzymes of aerobic respiratory chains, is fundamental to clarify the emergence of this important cellular process. Phylogenetic analyses of HCO O(2)Red have led to contradictory results, suggesting, in turn, that they predate oxygenic photosynthesis and already reduced oxygen as their function; they predate oxygenic photosynthesis, but did not reduce oxygen; they postdate oxygenic photosynthesis. Here, we present a discussion of current data on the distribution and phylogeny of HCO O(2)Red, which leads to a novel and clearer picture of the origin and evolution of these key enzymes as well as their function. PMID: 19647436 [PubMed - a... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2668320 Wed, 29 Jul 2009 23:00:00 +0100 2668320 http://www.medworm.com/index.php?rid=2668319&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19647437%26dopt%3DAbstract Authors: Colombini M The recently published 3D structures of the mitochondrial voltage-dependent anion-selective channel (VDAC) are almost identical to each other. However, they are in conflict with the results of biochemical and functional studies published in the past 18 years. Transmembrane folding patterns based on many biochemical and functional studies differ from the 3D structures in the exclusion of distinct transmembrane strands. These differences might be the consequence of changes observed in vitro that result in the formation of channels with the characteristic functional properties of VDAC. Is it possible to reconcile the discrepancies between the 3D structures and earlier models? As it was refolded from inclusion bodies, the protein used to obtain the 3D structures might ... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2668319 Wed, 29 Jul 2009 23:00:00 +0100 2668319 http://www.medworm.com/index.php?rid=2668324&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19646880%26dopt%3DAbstract Authors: van der Oost J, Jore MM, Westra ER, Lundgren M, Brouns SJ The recently discovered CRISPR (clustered regularly interspaced short palindromic repeat) defense system protects bacteria and archaea against mobile genetic elements. This immunity system has the potential to continuously adjust its reach at the genomic level, implying that both gain and loss of information is inheritable. The CRISPR system consists of typical stretches of interspaced repetitive DNA (CRISPRs) and associated cas genes. Three distinct stages are recognized in the CRISPR defense mechanism: (i) adaptation of the CRISPR via the integration of short sequences of the invaders as spacers; (ii) expression of CRISPRs and subsequent processing to small guide RNAs; and (iii) interference of target DNA by the crRNA... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2668324 Tue, 28 Jul 2009 23:00:00 +0100 2668324 http://www.medworm.com/index.php?rid=2556701&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19559620%26dopt%3DAbstract Authors: Holt IJ The mitochondrial genome is dwarfed by its neighbour in the nucleus, and, thus, it has been sensible for far more resources to be invested in the study of nuclear, rather than mitochondrial, DNA metabolism. Furthermore, few researchers have considered using mitochondrial DNA (mtDNA) as a model system for nuclear DNA metabolism. A quick look into the history of mtDNA provides ready answers as to why this was the case; however, recently mitochondria have been found to contain several nuclear replication and repair factors, so is there any potential to adopt the mitochondrion as a tool to unravel some of the intricacies of replication and repair in higher-order eukaryotes? Perhaps it is now time to invite the Cinderella genome to the ball. PMID: 19559620 [PubMed - as ... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2556701 Tue, 23 Jun 2009 23:00:00 +0100 2556701 http://www.medworm.com/index.php?rid=2556700&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19559621%26dopt%3DAbstract Authors: Campanella M, Parker N, Tan CH, Hall AM, Duchen MR When mitochondrial function is compromised and the mitochondrial membrane potential (Deltapsi(m)) falls below a threshold, the F(1)F(o)-ATP synthase can reverse, hydrolysing ATP to pump protons out of the mitochondrial matrix. Although this activity can deplete ATP and precipitate cell death, it is limited by the mitochondrial protein IF(1), an endogenous F(1)F(o)-ATPase inhibitor. IF(1), therefore, preserves ATP at the expense of Deltapsi(m). Despite a wealth of detailed knowledge on the biochemistry of the interaction of IF(1) and the F(1)F(o)-ATPase, little is known about its physiological activity. Emerging research suggests that IF(1) has a wider ranging impact on mitochondrial structure and function than previously thoug... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2556700 Tue, 23 Jun 2009 23:00:00 +0100 2556700 http://www.medworm.com/index.php?rid=2556699&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19559622%26dopt%3DAbstract Authors: Matenia D, Mandelkow EM Microtubule-affinity regulating kinases (MARKs) were originally discovered by their ability to phosphorylate tau protein and related microtubule-associated proteins (MAPs), and thereby to regulate microtubule dynamics in neurons. Members of the MARK (also known as partition-defective [Par]-1 kinase) family were subsequently found to be highly conserved and to have key roles in cell processes such as determination of polarity, cell-cycle control, intracellular signal transduction, transport and cytoskeleton. This is important for neuronal differentiation, but is also prominent in neurodegenerative 'tauopathies' such as Alzheimer's disease. The identified functions of MARK/Par-1 are diverse and require accurate regulation. Recent discoveries including the... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2556699 Tue, 23 Jun 2009 23:00:00 +0100 2556699 http://www.medworm.com/index.php?rid=2546782&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19546006%26dopt%3DAbstract Authors: Verspurten J, Gevaert K, Declercq W, Vandenabeele P Proteinases are enzymes that play important roles in vital cellular and extracellular processes by hydrolytically cleaving peptide bonds in their protein substrates. This cleavage can be non-specific as part of degradation during protein catabolism or highly specific as part of proteolytic cascades and signal transduction events. Several web tools are available for predicting possible cleavage sites in candidate substrates. Here, we compare existing prediction tools with SitePrediction, a novel and user-friendly tool for identifying potential cleavage sites. This prediction is based on known datasets found in the literature, stored in web-accessible repositories or generated by our own experiments. Comparison of the different... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2546782 Fri, 19 Jun 2009 23:00:00 +0100 2546782 http://www.medworm.com/index.php?rid=2546786&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19535250%26dopt%3DAbstract Authors: Lie PP, Cheng CY, Mruk DD Throughout spermatogenesis, a select pool of germ cells, the leptotene spermatocytes, must traverse the blood-testis barrier (BTB) to enter the adluminal compartment of the seminiferous epithelium. This event requires extensive restructuring of cell junctions, and it must also coincide with germ cell cycle progression in preparation for primary spermatocyte meiosis. Recent findings show that cell-cycle-associated kinases and phosphatases, including mitogen-activated protein kinases (MAPKs), participate in the pathways that also direct germ cell adhesion and movement. Our new biochemical model explains, in part, how two distinct cellular events, BTB restructuring and spermiation, are coordinated to maintain spermatogenesis and fertility. In this way, M... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2546786 Sun, 14 Jun 2009 23:00:00 +0100 2546786 http://www.medworm.com/index.php?rid=2546784&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19535251%26dopt%3DAbstract Authors: Mukhopadhyay R, Jia J, Arif A, Ray PS, Fox PL Functionally related genes are coregulated by specific RNA-protein interactions that direct transcript-selective translational control. In myeloid cells, interferon (IFN)-gamma induces formation of the heterotetrameric, IFN-gamma-activated inhibitor of translation (GAIT) complex comprising glutamyl-prolyl tRNA synthetase (EPRS), NS1-associated protein 1 (NSAP1), ribosomal protein L13a and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). This complex binds defined 3' untranslated region elements within a family of inflammatory mRNAs and suppresses their translation. IFN-gamma-dependent phosphorylation, and consequent release of EPRS and L13a from the tRNA multisynthetase complex and 60S ribosomal subunit, respectively, regulates GA... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2546784 Sun, 14 Jun 2009 23:00:00 +0100 2546784 http://www.medworm.com/index.php?rid=2546788&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19525115%26dopt%3DAbstract Authors: Lee DC, Jia Z Bacterial protein tyrosine (Tyr) phosphorylation emerged as an exciting new field of research in the last decade. Of known bacterial Tyr (BY) kinases, most regulate the production of pathogenic capsular and extracellular polysaccharide in both Gram-positive and Gram-negative bacteria. The recent publications of the first two BY kinase structures, Etk from Escherichia coli and CapB from Staphylococcus aureus, reveal that the 3D folds bear no resemblance to their mammalian counterparts but instead are similar to those of the MinD ATPases from the P-loop NTPase superfamily. These structural studies provided the first glimpse into the functional machinery of BY kinases, including their enzymatic specificity and unique activation mechanisms, which are unlike anything ... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2546788 Thu, 11 Jun 2009 23:00:00 +0100 2546788 http://www.medworm.com/index.php?rid=2546799&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19443222%26dopt%3DAbstract Authors: Temussi PA Sweet and bitter are taste qualities linked to food acceptance and rejection in humans. It was long thought that these taste sensations were closely related, but the discovery and characterization of taste receptors revealed that mammals express a single sweet receptor and many unrelated bitter receptors. Bitter-tasting chiral isomers of sweet compounds can bind to the umami receptor, rather than bitter receptors, and elicit the bitter sensation through crosstalk between labelled cells. In support of crosstalk between labelled cells, recent findings suggest that, although most receptor taste cells respond to only one taste, most presynaptic taste cells accept signals from labelled cells that respond to two or more different taste qualities. PMID: 19443222 [PubMe... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2546799 Sun, 31 May 2009 23:00:00 +0100 2546799 http://www.medworm.com/index.php?rid=2546797&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19446460%26dopt%3DAbstract Authors: Parthier C, Reedtz-Runge S, Rudolph R, Stubbs MT G-protein-coupled receptors (GPCRs) represent the largest constellation of validated drug targets. Crystal structures of class A GPCRs have facilitated major advances in understanding the principles underlying GPCR activation. By contrast, relatively little is known about class B GPCRs, a family of receptors for a variety of therapeutically relevant peptide hormones. Encouraging progress has recently been made through the structural elucidation of several extracellular hormone-binding domains of class B GPCRs in complex with their natural ligands or synthetic analogues. The structures reveal similar modes of ligand binding, with concomitant alpha-helical structuring of the ligand. The latter suggests an attractive mechanical mod... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2546797 Sun, 31 May 2009 23:00:00 +0100 2546797 http://www.medworm.com/index.php?rid=2546795&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19447626%26dopt%3DAbstract Authors: Chakrabarti O, Ashok A, Hegde RS Various fatal neurodegenerative disorders are caused by altered metabolism of the prion protein (PrP). These diseases are typically transmissible by an unusual 'protein-only' mechanism in which a misfolded isomer, PrP(Sc), confers its aberrant conformation onto normal cellular PrP. An impressive range of studies has investigated nearly every aspect of this fascinating event; yet, our understanding of how PrP(Sc) accumulation might lead to cellular dysfunction and neurodegeneration is trifling. Recent advances in our understanding of normal PrP biosynthesis and degradation might have unexpectedly shed new light on this complex problem. Indeed, our current understanding of normal PrP cell biology, coupled with a growing appreciation of its comple... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2546795 Sun, 31 May 2009 23:00:00 +0100 2546795 http://www.medworm.com/index.php?rid=2546793&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19447627%26dopt%3DAbstract Authors: Bouska A, Eischen CM The oncoprotein murine double minute 2 (Mdm2) is frequently overexpressed in many types of human malignancies. Although Mdm2 has an essential role in negatively regulating the p53 tumor suppressor, it also has less well characterized p53-independent functions that influence pathways that are crucial for controlling tumorigenesis. In addition to the impact Mdm2 has on p53-independent apoptosis, mounting evidence is linking increased Mdm2 levels to altered cell-cycle regulation, DNA replication and DNA repair leading to loss of genome stability. Mdm2 involvement in pathways that influence chromosome stability and cell death, distinct from its role in the p53 pathway, strengthens the position of Mdm2 as a desirable therapeutic target for the treatment of huma... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2546793 Sun, 31 May 2009 23:00:00 +0100 2546793 http://www.medworm.com/index.php?rid=2546792&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19464896%26dopt%3DAbstract Authors: Vermeulen L, Berghe WV, Beck IM, De Bosscher K, Haegeman G Among the mitogen-activated protein kinase (MAPK) targets, MSKs (mitogen- and stress-activated protein kinases) comprise a particularly interesting protein family. Because MSKs can be activated by both extracellular-signal-regulated kinase and p38 MAPKs, they are activated by many physiological and pathological stimuli. About ten years after their original discovery, they have been recognized as versatile kinases regulating gene transcription at multiple levels. MSKs directly target transcription factors, such as cAMP-response-element-binding protein and nuclear factor-kappaB, thereby enhancing their transcriptional activity. They also induce histone phosphorylation, which is accompanied by chromatin relaxation and fac... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2546792 Sun, 31 May 2009 23:00:00 +0100 2546792 http://www.medworm.com/index.php?rid=2546790&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19467874%26dopt%3DAbstract Authors: Veeramani S, Lee MS, Lin MF Although classical protein tyrosine phosphatase (PTP) superfamily members are cysteine-dependent, emerging evidence shows that many acid phosphatases (AcPs) function as histidine-dependent PTPs in vivo. These AcPs dephosphorylate phospho-tyrosine substrates intracellularly and could have roles in development and disease. In contrast to cysteine-dependent PTPs, they utilize histidine, rather than cysteine, for substrate dephosphorylation. Structural analyses reveal that active site histidine, but not cysteine, faces towards the substrate and functions as the phosphate acceptor. Nonetheless, during dephosphorylation, both histidine-dependent and cysteine-dependent PTPs use their active site arginine and aspartate for substrate binding and proton donat... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2546790 Sun, 31 May 2009 23:00:00 +0100 2546790 http://www.medworm.com/index.php?rid=2546811&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19362002%26dopt%3DAbstract Authors: Vos WL, Nazarov PV, Koehorst RB, Spruijt RB, Hemminga MA The major coat protein of the filamentous bacteriophage M13 is a surprising protein because it exists both as a membrane protein and as part of the M13 phage coat during its life cycle. Early studies showed that the phage-bound structure of the coat protein was a continuous I-shaped alpha-helix. However, throughout the years various structural models, both I-shaped and L-shaped, have been proposed for the membrane-bound state of the coat protein. Recently, site-directed labelling approaches have enabled the study of the coat protein under conditions that more closely mimic the in vivo membrane-bound state. Interestingly, the structure that has emerged from this work is I-shaped and similar to the structure in the phage-b... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2546811 Thu, 30 Apr 2009 23:00:00 +0100 2546811 http://www.medworm.com/index.php?rid=2546810&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19362484%26dopt%3DAbstract Authors: Shneider AM In this article I propose the classification of the evolutionary stages that a scientific discipline evolves through and the type of scientists that are the most productive at each stage. I believe that each scientific discipline evolves sequentially through four stages. Scientists at stage one introduce new objects and phenomena as subject matter for a new scientific discipline. To do this they have to introduce a new language adequately describing the subject matter. At stage two, scientists develop a toolbox of methods and techniques for the new discipline. Owing to this advancement in methodology, the spectrum of objects and phenomena that fall into the realm of the new science are further understood at this stage. Most of the specific knowledge is generated at... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2546810 Thu, 30 Apr 2009 23:00:00 +0100 2546810 http://www.medworm.com/index.php?rid=2546809&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19362843%26dopt%3DAbstract Authors: Kapanidis AN, Strick T Single-molecule techniques have moved from being a fascinating curiosity to a highlight of life science research. The single-molecule approach to biology offers distinct advantages over the conventional approach of taking bulk measurements; this additional information content usually comes at the cost of the additional complexity. Popular single-molecule methods include optical and magnetic tweezers, atomic force microscopy, tethered particle motion and single-molecule fluorescence spectroscopy; the complement of these methods offers a wide range of spatial and temporal capabilities. These approaches have been instrumental in addressing important biological questions in diverse areas such as protein-DNA interactions, protein folding and the function(s) o... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2546809 Thu, 30 Apr 2009 23:00:00 +0100 2546809 http://www.medworm.com/index.php?rid=2546807&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19375328%26dopt%3DAbstract Authors: Mimitou EP, Symington LS Homologous recombination (HR)-mediated DNA double-strand break repair maintains genome integrity. Although long-studied, an understanding of two essential steps in this process -- the resection of DNA ends to produce recombinogenic 3' single-stranded DNA tails and the resolution of recombination intermediates -- has remained elusive. Recent findings show an unexpected role for the Sgs1 (BLM) helicase and Dna2 nuclease in end resection, and provide mechanistic insight into the initiation of 5'-3' resection as well as its regulation by the cell cycle and the DNA damage response. Moreover, the identification of a novel Holliday junction resolvase, Yen1 (GEN1), and several helicases that dismantle strand invasion intermediates has increased the repertoire ... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2546807 Thu, 30 Apr 2009 23:00:00 +0100 2546807 http://www.medworm.com/index.php?rid=2546805&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19375329%26dopt%3DAbstract Authors: van Gent DC Correct joining of broken chromosomes is indispensable to prevent cell death, ageing and cancer. Two recent papers highlight the importance of p53-binding protein 1 (53BP1) in connecting distant sites in T-cell receptor loci and dysfunctional telomeres. These studies refine our understanding of the specific subset of DNA double-strand breaks that require the accessory end-joining factor 53BP1. PMID: 19375329 [PubMed - in process] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2546805 Thu, 30 Apr 2009 23:00:00 +0100 2546805 http://www.medworm.com/index.php?rid=2546803&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19376708%26dopt%3DAbstract Authors: Connolly K, Culver G The ribosome is an essential ribonucleoprotein enzyme, and its biogenesis is a fundamental process in all living cells. Recent X-ray crystal structures of the bacterial ribosome and new technologies have allowed a greater interrogation of in vitro ribosome assembly; however, substantially less is known about ribosome biogenesis in vivo. Ongoing investigations are focused on elucidating the cellular processes that facilitate biogenesis of the ribosomal subunits, and many extraribosomal factors, including modification enzymes, remodeling enzymes and GTPases, are being uncovered. Moreover, specific roles for ribosome biogenesis factors in subunit maturation are now being elaborated. Ultimately, such studies will reveal a more complete understanding of process... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2546803 Thu, 30 Apr 2009 23:00:00 +0100 2546803 http://www.medworm.com/index.php?rid=2546801&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19376709%26dopt%3DAbstract Authors: Hirsch E, Braccini L, Ciraolo E, Morello F, Perino A Class I phosphoinositide 3-kinases (PI3Ks) are heterodimeric enzymes involved in signal transduction triggered by growth factors and G-protein-coupled receptors. The catalytic function of PI3Ks is well known to promote a wide variety of biological processes, including proliferation, survival and migration, but a new layer of complexity in the function of PI3Ks has recently emerged, indicating that these proteins function not only as kinases but also as scaffold proteins. Knockout mice that lack PI3K protein expression show a different phenotype from knock-in mice expressing PI3K mutants that have lost their kinase activity, providing evidence for this novel role of PI3Ks. We will discuss such findings, highlighting the cruci... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2546801 Thu, 30 Apr 2009 23:00:00 +0100 2546801 http://www.medworm.com/index.php?rid=2324043&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19359180%26dopt%3DAbstract Authors: Neckers L, Mollapour M, Tsutsumi S Hsp90 chaperone function requires traversal of a nucleotide-dependent conformational cycle, but the slow and variable rate of Hsp90-mediated ATP hydrolysis is difficult to envision as a determinant of conformational change. A recent study solves this dilemma by showing that Hsp90 samples multiple conformational states in the absence of nucleotides, which serve to influence, but not direct, the cycle. The conformational program of Hsp90 is conserved from bacteria to humans, although the population dynamics are species specific. PMID: 19359180 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2324043 Tue, 07 Apr 2009 04:00:00 +0100 2324043 http://www.medworm.com/index.php?rid=2324042&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19359181%26dopt%3DAbstract Authors: Summers DW, Douglas PM, Ramos CH, Cyr DM Heat shock protein 40 (Hsp40) co-chaperones assist in cellular protein folding and degradation through the binding and delivery of non-native proteins to heat shock protein 70 (Hsp70). The mechanism for substrate transfer from Hsp40s to Hsp70 is unknown. Two recent studies provide new details that shed light on novel mechanisms for substrate recognition by Hsp40s and a common mechanism for polypeptide transfer to Hsp70. PMID: 19359181 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2324042 Tue, 07 Apr 2009 04:00:00 +0100 2324042 http://www.medworm.com/index.php?rid=2295809&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19321346%26dopt%3DAbstract Authors: Hayes JD, McMahon M Transcription factor nuclear factor-erythroid 2-related factor 2 (NRF2) controls cellular adaptation to oxidants and electrophiles by inducing antioxidant and detoxification genes in response to redox stress. NRF2 is negatively regulated by Kelch-like ECH-associated protein 1 (KEAP1). Tumours from approximately 15% of patients with lung cancer harbour somatic mutations in KEAP1 that prevent effective NRF2 repression. Recently, two NRF2 mutation 'hot-spots' were identified in approximately 10% of patients with lung cancer, enabling the transcription factor to evade KEAP1-mediated repression. Somatic mutations in KEAP1 and NRF2 provide an insight into the molecular mechanisms by which NRF2 is regulated. Moreover, constitutive NRF2 activation might cause drug ... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2295809 Mon, 23 Mar 2009 04:00:00 +0100 2295809 http://www.medworm.com/index.php?rid=2295813&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19303305%26dopt%3DAbstract Authors: Mulkidjanian AY, Galperin MY, Koonin EV Studies of the past several decades have provided major insights into the structural organization of biological membranes and mechanisms of many membrane molecular machines. However, the origin(s) of the membrane(s) and membrane proteins remains enigmatic. We discuss different concepts of the origin and early evolution of membranes with a focus on the evolution of the (im)permeability to charged molecules such as proteins, nucleic acids and small ions. Reconstruction of the evolution of F-type and A/V-type membrane ATPases (ATP synthases), which are either proton- or sodium-dependent, might help us to understand not only the origin of membrane bioenergetics but also of membranes themselves. We argue that evolution of biological membranes... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2295813 Wed, 18 Mar 2009 04:00:00 +0100 2295813 http://www.medworm.com/index.php?rid=2283237&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19299141%26dopt%3DAbstract Authors: Michel F, Costa M, Westhof E Group II introns contain a large ribozyme, which catalyzes self-splicing, and the coding sequence of a reverse transcriptase, the function of which is to cooperate with the ribozyme to achieve genomic mobility. Despite its lack of substrates for both steps of the splicing process, the crystal structure of a group II ribozyme reveals the location of two metal ions most likely to be involved in catalysis; the RNA structure that binds to these ions results from the bending of a local motif by the folding of the rest of the ribozyme. The stage is now set to determine where the intron-encoded protein binds to its partner and whether the spliceosome uses a counterpart of the group II catalytic center to excise nuclear pre-messenger introns. PMID: 192... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2283237 Tue, 17 Mar 2009 04:00:00 +0100 2283237 http://www.medworm.com/index.php?rid=2283236&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19299142%26dopt%3DAbstract Authors: Hernández G The Shine-Dalgarno sequence of prokaryotic mRNAs, which helps to bind and position the ribosome at the start site for protein synthesis, is absent from eukaryotic mRNAs. Instead, for most, a structure at the 5' end and a much larger number of protein initiation factors are needed for both binding of the ribosome and for successful start-site selection, that is, a 'cap-dependent' initiation mechanism. Although the mechanics of this process are well studied, what is not clear is how it evolved. By analyzing recent progress in different fields, I suggest that it was the need to adjust to the arrival of the nuclear membrane and the subsequent requirement to export intron-less mRNAs to the cytoplasm that spurred the shift to the more complex translation initiation ... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2283236 Tue, 17 Mar 2009 04:00:00 +0100 2283236 http://www.medworm.com/index.php?rid=2283235&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19299143%26dopt%3DAbstract Authors: Kok K, Geering B, Vanhaesebroeck B Both the biology and the therapeutic potential of the phosphoinositide 3-kinase (PI3K) signalling axis have been the subject of intense investigation; however, little is known about the regulation of PI3K expression. Emerging evidence indicates that PI3K levels change in response to cellular stimulation with insulin and nuclear receptor ligands, and during various physiological and pathological processes including differentiation, regeneration, hypertension and cancer. Recently identified mechanisms that control PI3K production include increased gene copy number in cancer, and transcriptional regulation of the p110alpha PI3K gene by FOXO3a, NF-kappaB and p53, and of the PI3K regulatory subunits by STAT3, EBNA-2 and SREBP. In most instances, h... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2283235 Tue, 17 Mar 2009 04:00:00 +0100 2283235 http://www.medworm.com/index.php?rid=2268451&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19282181%26dopt%3DAbstract Authors: Demartino GN Most eukaryotic proteins are degraded by the 26S proteasome as a consequence of their covalent modification with ubiquitin. Although the proteasome is found in some prokaryotes, ubiquitin is not, which indicates that substrates are targeted to prokaryotic proteasomes by a fundamentally different mechanism. A recent study has identified Pup (prokaryotic ubiquitin-like protein) as a mycobacterial protein that functions in a manner analogous to ubiquitin for proteasome-dependent proteolysis in prokaryotes. PMID: 19282181 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2268451 Tue, 10 Mar 2009 04:00:00 +0100 2268451 http://www.medworm.com/index.php?rid=2268386&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19282182%26dopt%3DAbstract Authors: Kobor MS, Lorincz MC DNA methylation state and the composition of the nucleosome core particle influence chromatin structure and, in turn, transcriptional competence. Although it is clear that chromatin remodeling and covalent histone modifications regulate DNA methylation in plants and animals, the role of histone variants in directing DNA methylation, and vice versa, has not been addressed. A new genome-wide study in Arabidopsis thaliana reveals a broadly antagonistic relationship between H2A.Z occupancy and DNA methylation. PMID: 19282182 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2268386 Tue, 10 Mar 2009 04:00:00 +0100 2268386 http://www.medworm.com/index.php?rid=2268291&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19282183%26dopt%3DAbstract Authors: Sarge KD, Park-Sarge OK Covalent modification by SUMO polypeptides, or sumoylation, is an important regulator of the functional properties of many proteins. Among these are several proteins implicated in human diseases including cancer, Huntington's, Alzheimer's, and Parkinson's diseases, as well as spinocerebellar ataxia 1 and amyotrophic lateral sclerosis. Recent reports reveal two new examples of human disease-associated proteins that are SUMO modified: amyloid precursor protein and lamin A. These findings point to a function for sumoylation in modulating amyloid-beta peptide levels, indicating a potential role in Alzheimer's disease, and for decreased lamin A sumoylation as a causative factor in familial dilated cardiomyopathy. PMID: 19282183 [PubMed - as supplied by p... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2268291 Tue, 10 Mar 2009 04:00:00 +0100 2268291 http://www.medworm.com/index.php?rid=2257663&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19269830%26dopt%3DAbstract Authors: Ryo A, Wulf G, Lee TH, Lu KP SMRT (silencing mediator for retinoic acid and thyroid hormone receptors) is a transcriptional co-repressor that mediates the repressive function of nuclear hormone receptors such as the estrogen receptor (ER). Decreased SMRT levels correlate with acquired tamoxifen resistance in breast cancer, and SMRT restoration might resensitize breast cancer cells to tamoxifen. A new study demonstrates that SMRT protein stability is regulated by phosphorylation-dependent Pin1-catalyzed prolyl-isomerization. Pin1 functions downstream of HER2, positioning it as an important modulator of the crosstalk between ER and growth factor signaling. PMID: 19269830 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2257663 Fri, 06 Mar 2009 05:00:00 +0100 2257663 http://www.medworm.com/index.php?rid=2211441&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19233655%26dopt%3DAbstract Authors: Nelson TJ, Alkon DL Protein kinase C (PKC) activators possess potent neurotrophic and neuroprotective activity, thus indicating potential applications in treating neurodegenerative diseases, stroke and traumatic brain injury. Although some activators, such as bryostatin and gnidimacrin, have been tested as antitumor agents, others, such as phorbol esters, are potent tumor promoters. All PKC activators downregulate PKC at high concentrations and long application times. However, tumorigenic activators downregulate certain PKC isozymes, especially PKCdelta, more strongly. Tumorigenic activators possess unique structural features that could account for this difference. At concentrations that minimize PKC downregulation, PKC activators can improve long-term memory, reduce beta-amyl... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2211441 Fri, 20 Feb 2009 05:00:00 +0100 2211441 http://www.medworm.com/index.php?rid=2211440&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19233656%26dopt%3DAbstract Authors: Brennan DF, Barford D We propose the classification of a protein post-translational modification, eliminylation, based on the recently delineated mechanism of the Shigella OspF and Salmonella SpvC phosphothreonine lyases. These bacterial type-III secretion-system virulence factors are injected into eukaryotic cells and inhibit signalling by irreversibly inactivating mitogen-activated protein kinases (MAPKs). Remarkably, they employ an unusual beta-elimination reaction, removing the phosphate from phosphothreonine and converting it into dehydrobutyrine (an alkene). Eliminylated cysteine can also be produced by decarboxylation and eliminylated serine and threonine by dehydration; these residues are found in the eye lens and in bacterial lantibiotics. We postulate that eliminylat... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2211440 Fri, 20 Feb 2009 05:00:00 +0100 2211440 http://www.medworm.com/index.php?rid=2211439&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19233657%26dopt%3DAbstract Authors: Renner F, Schmitz ML After nuclear factor (NF)-kappaB activation, a complex network of negative feedback loops ensures that the termination of the NF-kappaB response occurs in a highly organized manner. Recent results show that signals initiated during the induction phase already program a default termination procedure that enables temporally and spatially regulated NF-kappaB deactivation. All negative feedback mechanisms occur with a characteristic time delay, thereby permitting full NF-kappaB function during the interim period. Some proteins that direct termination are produced directly in response to NF-kappaB activation, whereas others are activated via inducible binding or by protein stabilization. Another time-delaying strategy of NF-kappaB feedback inhibitory proteins r... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2211439 Fri, 20 Feb 2009 05:00:00 +0100 2211439 http://www.medworm.com/index.php?rid=2211442&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19230677%26dopt%3DAbstract Authors: Hodis E, Sussman JL PMID: 19230677 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2211442 Mon, 16 Feb 2009 05:00:00 +0100 2211442 http://www.medworm.com/index.php?rid=2191071&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19217300%26dopt%3DAbstract Authors: Berndt JD, Moon RT, Major MB Numerous studies have pointed to interactions between the tumor suppressor von Hippel-Lindau (VHL) and the oncogenic Wnt-beta-catenin signaling cascade; however, the mechanism of this crosstalk has remained elusive. Among other roles, VHL can promote the stabilization of Jade-1. Now, recent findings provide compelling evidence that Jade-1 ubiquitylates beta-catenin, leading to its degradation. Thus, the loss of VHL, as seen in clear cell renal cell carcinoma, could lead to tumor formation through beta-catenin de-repression. PMID: 19217300 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2191071 Wed, 11 Feb 2009 05:00:00 +0100 2191071 http://www.medworm.com/index.php?rid=2183173&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19208481%26dopt%3DAbstract Authors: Biamonti G, Caceres JF In response to physical and chemical stresses that affect protein folding and, thus, the execution of normal metabolic processes, cells activate gene-expression strategies aimed at increasing their chance of survival. One target of several stressing agents is pre-mRNA splicing, which is inhibited upon heat shock. Recently, the molecular basis of this splicing inhibition has begun to emerge. Interestingly, different mechanisms seem to be in place to block constitutive pre-mRNA splicing and to affect alternative splicing regulation. This could be important to modulate gene expression during recovery from stress. Thus, pre-mRNA splicing emerges as a central mechanism to integrate cellular and metabolic stresses into gene-expression profiles. PMID: 19208... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2183173 Sat, 07 Feb 2009 05:00:00 +0100 2183173 http://www.medworm.com/index.php?rid=2156960&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19181528%26dopt%3DAbstract Authors: Marabotti A, Facchiano A PMID: 19181528 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2156960 Fri, 30 Jan 2009 05:00:00 +0100 2156960 http://www.medworm.com/index.php?rid=2138163&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19168360%26dopt%3DAbstract Authors: Brady GF, Duckett CS Apoptosis is a highly conserved form of cell death that is essential for controlling cell numbers throughout the lifetime of an organism. In Caenorhabditis elegans, the final step in the apoptotic cascade is activation of the death-inducing protease CED-3. Until now, no direct negative regulators of CED-3 had been identified, so the mechanism for maintaining a proper life-death balance was unclear. Now, a new study identifies CSP-3 as an important negative regulator of CED-3 during C. elegans development. PMID: 19168360 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2138163 Fri, 23 Jan 2009 05:00:00 +0100 2138163 http://www.medworm.com/index.php?rid=2101506&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19135374%26dopt%3DAbstract Authors: Dalle-Donne I, Rossi R, Colombo G, Giustarini D, Milzani A S-Glutathionylation is the specific post-translational modification of protein cysteine residues by the addition of the tripeptide glutathione, the most abundant and important low-molecular-mass thiol within most cell types. Protein S-glutathionylation is promoted by oxidative or nitrosative stress but also occurs in unstressed cells. It can serve to regulate a variety of cellular processes by modulating protein function and to prevent irreversible oxidation of protein thiols. Recent findings support an essential role for S-glutathionylation in the control of cell-signalling pathways associated with viral infections and with tumour necrosis factor-(-induced apoptosis. Glyceraldehyde-3-phosphate dehydrogenase has recent... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2101506 Wed, 07 Jan 2009 05:00:00 +0100 2101506 http://www.medworm.com/index.php?rid=2061641&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19101147%26dopt%3DAbstract Authors: Leis A, Rockel B, Andrees L, Baumeister W Cryogenic electron tomography (cryo- ET) enables the 3D visualization of biological material at a previously unseeable scale. Carefully controlled cryogenic specimen preparation avoids the artefacts that are notorious to conventional electron microscopy specimen preparation. To date, studies employing cryo- ET have mostly been restricted to isolated macromolecular assemblies, small prokaryotic cells or thin regions of eukaryotic cells owing to the limited penetration depth of electrons through ice-embedded preparations. Recent progress in cryosectioning makes it possible to acquire tomograms from many kinds of vitrified cells and tissues. The systematic and comprehensive interpretation of such tomograms will provide unprecedented insig... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2061641 Thu, 18 Dec 2008 05:00:00 +0100 2061641 http://www.medworm.com/index.php?rid=2027867&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19058968%26dopt%3DAbstract Authors: Morona R, Purins L, Tocilj A, Matte A, Cygler M Polysaccharides are ubiquitously distributed on the cell surface of bacteria. These polymers are involved in many processes, including immune avoidance and bacteria-host interactions, which are especially important for pathogenic organisms. In many instances, the lengths of these polysaccharides are not random, but rather distribute around some mean value, termed the modal length. A large family of proteins, called polysaccharide co-polymerases (PCPs), found in both Gram-negative and Gram-positive species regulate polysaccharide modal length. Recent crystal structures of Wzz proteins from Escherichia coli and Salmonella typhimurium provide the first atomic-resolution information for one family of PCPs, the PCP1 group. These cryst... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2027867 Thu, 04 Dec 2008 05:00:00 +0100 2027867 http://www.medworm.com/index.php?rid=2027866&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19062292%26dopt%3DAbstract Authors: Conaway RC, Conaway JW The Ino80 ATPase is a member of the SNF2 family of ATPases and functions as an integral component of a multisubunit ATP-dependent chromatin remodeling complex. Although INO80 complexes from yeast and higher eukaryotes share a common core of conserved subunits, the complexes have diverged substantially during evolution and have acquired new subunits with apparently species-specific functions. Recent studies have shown that the INO80 complex contributes to a wide variety of chromatin-dependent nuclear transactions, including transcription, DNA repair and DNA replication. PMID: 19062292 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2027866 Thu, 04 Dec 2008 05:00:00 +0100 2027866 http://www.medworm.com/index.php?rid=2027865&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19062293%26dopt%3DAbstract Authors: Tokuriki N, Oldfield CJ, Uversky VN, Berezovsky IN, Tawfik DS Natural selection shapes the sequence, structure and biophysical properties of proteins to fit their environment. We hypothesize that highly thermostable proteins and viral proteins represent two opposing adaptation strategies. Thermostable proteins are highly compact and possess well-packed hydrophobic cores and intensely charged surfaces. By contrast, viral proteins, and RNA viral proteins in particular, display a high occurrence of disordered segments and loosely packed cores. These features might endow viral proteins with increased structural flexibility and effective ways to interact with the components of the host. They could also be related to high adaptability levels and mutation rates observed in viruses, t... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=2027865 Wed, 03 Dec 2008 05:00:00 +0100 2027865 http://www.medworm.com/index.php?rid=1999362&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19038550%26dopt%3DAbstract Authors: Auble DT TATA-binding protein (TBP) is a central component of the transcription apparatus and its association with promoters is dynamically regulated genome-wide. Recent work has shed new light on the functional specificity of Mot1 and NC2, two factors that control TBP distribution and activity. These studies underscore how regulation of TBP globally influences fundamental aspects of gene expression, including the balance of transcriptional output from different types of promoters, and the amplitude and timing of gene activation. PMID: 19038550 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1999362 Tue, 25 Nov 2008 05:00:00 +0100 1999362 http://www.medworm.com/index.php?rid=1991678&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19028099%26dopt%3DAbstract Authors: Welch GR PMID: 19028099 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1991678 Fri, 21 Nov 2008 05:00:00 +0100 1991678 http://www.medworm.com/index.php?rid=1981337&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19019685%26dopt%3DAbstract Authors: Fuxreiter M, Tompa P PMID: 19019685 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1981337 Mon, 17 Nov 2008 05:00:00 +0100 1981337 http://www.medworm.com/index.php?rid=1964362&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19008105%26dopt%3DAbstract Authors: Mattson MP, Ashery U In Alzheimer's disease (AD), neurons suffer dysfunction and death associated with aberrant tau phosphorylation and subsequent neurofibrillary tangles. A new study reveals a surprising neuroprotective role for a truncated p73 isoform (DeltaNp73). Aged mice with reduced DeltaNp73 levels exhibit tau pathology and cognitive deficits, and DeltaNp73 reduction in mice with amyloid pathology causes extensive tangle formation and neuron death. These findings provide a novel animal model of AD and a potential therapeutic role for DeltaNp73 inducers. PMID: 19008105 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1964362 Wed, 12 Nov 2008 05:00:00 +0100 1964362 http://www.medworm.com/index.php?rid=1964361&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19008106%26dopt%3DAbstract Authors: Doyle SM, Wickner S Heat-shock protein 104 (Hsp104) and caseinolytic peptidase B (ClpB), members of the AAA+ superfamily, are molecular machines involved in disaggregating insoluble protein aggregates, a process not long ago thought to be impossible. During extreme stress they are essential for cell survival. In addition, Hsp104 regulates prion assembly and disassembly. For most of their protein remodeling activities Hsp104 and ClpB work in collaboration with the Hsp70 or DnaK chaperone systems. Together, the two chaperones catalyze protein disaggregation and reactivation by a mechanism probably involving the extraction of polypeptides from aggregates by forced unfolding and translocation through the Hsp104/ClpB central cavity. The polypeptides are then released back into the ... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1964361 Tue, 11 Nov 2008 05:00:00 +0100 1964361 http://www.medworm.com/index.php?rid=1964360&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19008107%26dopt%3DAbstract Authors: Ducluzeau AL, van Lis R, Duval S, Schoepp-Cothenet B, Russell MJ, Nitschke W Evolutionary histories of enzymes involved in chemiosmotic energy conversion indicate that a strongly oxidizing substrate was available to the last universal common ancestor before the divergence of Bacteria and Archaea. According to palaeogeochemical evidence, O(2) was not present beyond trace amounts on the early Earth. Based on recent phylogenetic, enzymatic and geochemical results, we propose that, in the earliest Archaean, nitric oxide (NO) and its derivatives nitrate and nitrite served as strongly oxidizing substrates driving the evolution of a bioenergetic pathway related to modern dissimilatory denitrification. Aerobic respiration emerged later from within this ancestral pathway via adaptation... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1964360 Tue, 11 Nov 2008 05:00:00 +0100 1964360 http://www.medworm.com/index.php?rid=1952431&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18996013%26dopt%3DAbstract Authors: Komar AA A unifying concept that combines the basic features governing self-organization of proteins into complex three-dimensional structures in vitro and in vivo is still lacking. Recent experimental results and theoretical in silico modeling studies provide evidence showing that mRNA might contain an additional layer of information, beyond the amino acid sequence, that fine-tunes in vivo protein folding, which is largely believed to start as a co-translational process. These findings indicate that translation kinetics might direct the co-translational folding pathway and that translational pausing at rare codons might provide a time delay to enable independent and sequential folding of the defined portions of the nascent polypeptide emerging from the ribosome. PMID: 189... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1952431 Thu, 06 Nov 2008 05:00:00 +0100 1952431 http://www.medworm.com/index.php?rid=1952430&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18996014%26dopt%3DAbstract Authors: Silva JL, Lima LM, Foguel D, Cordeiro Y PMID: 18996014 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1952430 Thu, 06 Nov 2008 05:00:00 +0100 1952430 http://www.medworm.com/index.php?rid=1952429&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18996015%26dopt%3DAbstract Authors: Pinotsis N, Abrusci P, Djinović-Carugo K, Wilmanns M The contraction-relaxation cycle of muscle cells translates into large movements of several filament systems in sarcomeres, requiring special molecular mechanisms to maintain their structural integrity. Recent structural and functional data from three filaments harboring extensive arrays of immunoglobulin-like domains - titin, filamin and myomesin - have, for the first time, unraveled a common function of their terminal domains: assembly and anchoring of the respective filaments. In each case, the protein-protein interactions are mediated by antiparallel dimerization modules via intermolecular beta-sheets. These observations on terminal filament assembly indicate an attractive model for several other filament proteins ... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1952429 Thu, 06 Nov 2008 05:00:00 +0100 1952429 http://www.medworm.com/index.php?rid=1952428&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18996016%26dopt%3DAbstract Authors: Radulescu RT, Brenig B PMID: 18996016 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1952428 Thu, 06 Nov 2008 05:00:00 +0100 1952428 http://www.medworm.com/index.php?rid=1945479&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18990579%26dopt%3DAbstract Authors: Lembo D, Brune W Ribonucleotide reductase (RNR), a crucial enzyme for nucleotide anabolism, is encoded by all living organisms and by large DNA viruses such as the herpesviruses. Surprisingly, the beta-herpesvirus subfamily RNR R1 subunit homologues are catalytically inactive and their function remained enigmatic for many years. Recent work sheds light on the function of M45, the murine cytomegalovirus R1 homologue; during viral evolution, M45 apparently lost its original RNR activity but gained the ability, via inhibiting RIP1, a cellular adaptor protein, to block cellular signaling pathways involved in innate immunity and inflammation. The discovery of this novel mechanism of viral immune subversion provides further support to the concept of evolutionary tinkering. PMID:... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1945479 Tue, 04 Nov 2008 05:00:00 +0100 1945479 http://www.medworm.com/index.php?rid=1902125&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18945619%26dopt%3DAbstract Authors: Csermely P Active centres and hot spots of proteins have a paramount importance in enzyme action, protein-complex formation and drug design. Recently, several publications successfully applied the analysis of residue networks to predict active centres in proteins. Most real-world networks show several properties, such as small-worldness or scale-free degree distribution, which are rather general features of networks, from molecules to society at large. Using analogy, I propose that existing findings and methodology already enable us to detect active centres in cells and can be expanded to social networks and ecosystems. Members of these active centres are termed here as 'creative elements' of their respective networks, which can help them to survive unprecedented, novel challe... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1902125 Mon, 20 Oct 2008 04:00:00 +0100 1902125 http://www.medworm.com/index.php?rid=1895640&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18938082%26dopt%3DAbstract Authors: Hooley P, Whitehead MP, Brown MR Polyphosphate (poly P) is a polymer of up to several hundred phosphate residues and is important to a variety of cell processes. The main poly P synthetic enzyme in many bacteria is poly P kinase 1 (PPK1), which until recently had been detected among eukaryotes in some protists only. There is now evidence for the presence in several other eukaryotes of PPK1 homologues and also a second bacteria-type enzyme, PPK2. The latest genome databases reveal that the 'Kornberg' enzyme complex of three actin-related proteins, termed DdPPK2 in Dictyostelium discoideum, might also be ubiquitous in eukaryotes. Owing to the intimate association of poly P synthesis with the formation of structural fibres, this ubiquity indicates a central role for this molecule... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1895640 Sat, 18 Oct 2008 04:00:00 +0100 1895640 http://www.medworm.com/index.php?rid=1895641&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18929489%26dopt%3DAbstract Authors: Shaw RJ mTOR (mammalian target of rapamycin) is a highly conserved nutrient-responsive regulator of cell growth that is found in all eukaryotes. The mechanism by which amino acids signal to mTOR has remained one of the largest outstanding questions in the field. Two recent complimentary studies provide compelling evidence that the Rag family of small GTPases is both necessary and sufficient to transmit a positive signal from amino acids to mTOR. PMID: 18929489 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1895641 Wed, 15 Oct 2008 04:00:00 +0100 1895641 http://www.medworm.com/index.php?rid=1888527&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18926707%26dopt%3DAbstract Authors: Wei N, Serino G, Deng XW The COP9 signalosome (CSN) is a conserved protein complex that functions in the ubiquitin-proteasome pathway. After two decades of research, we now know that the CSN is a multi-subunit protease that regulates the activity of cullin-RING ligase (CRL) families of ubiquitin E3 complexes. The CSN is rapidly emerging as a key player in the DNA-damage response, cell-cycle control and gene expression. The independent functions of CSN5 (also known as JAB1) add to the complexity of the CSN machinery. Here, we provide an updated view of the structure, functions and regulation of this protein complex. PMID: 18926707 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1888527 Tue, 14 Oct 2008 04:00:00 +0100 1888527 http://www.medworm.com/index.php?rid=1888526&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18926708%26dopt%3DAbstract Authors: Bohr VA The RecQ helicases are guardians of the genome. Members of this conserved family of proteins have a key role in protecting and stabilizing the genome against deleterious changes. Deficiencies in RecQ helicases can lead to high levels of genomic instability and, in humans, to premature aging and increased susceptibility to cancer. Their diverse roles in DNA metabolism, which include a role in telomere maintenance, reflect interactions with multiple cellular proteins, some of which are multifunctional and also have very diverse functions. The results of in vitro cellular and biochemical studies have been complimented by recent in vivo studies using genetically modified mouse strains. Together, these approaches are helping to unravel the mechanism(s) of action and biologi... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1888526 Tue, 14 Oct 2008 04:00:00 +0100 1888526 http://www.medworm.com/index.php?rid=1880202&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18848452%26dopt%3DAbstract Authors: Aberdam D, Candi E, Knight RA, Melino G The epidermis and its appendages provide organisms with protection from the environment, keeping pathogens out and preventing the loss of essential body fluids. To perform both functions, the skin has elaborated a complex differentiation process known as cornification. The renewal capacity of the skin, which is responsible for maintaining tissue homeostasis, regenerating hair and repairing the epidermis after injury, resides in the basal proliferating compartment in which epidermal stem cells are located. These cells possess the remarkable capacity to both self-perpetuate and give rise to the differentiating cells that form mature tissues. Recent findings indicate that microRNAs have an essential role in orchestrating the formation of ep... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1880202 Wed, 08 Oct 2008 04:00:00 +0100 1880202 http://www.medworm.com/index.php?rid=1880201&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18848453%26dopt%3DAbstract Authors: Robinson MW, Dalton JP, Donnelly S Helminth pathogens express papain-like cysteine peptidases, termed cathepsins, which have important roles in virulence, including host entry, tissue migration and the suppression of host immune responses. The liver fluke Fasciola hepatica, an emerging human pathogen, expresses the largest cathepsin L cysteine protease family yet described. Recent phylogenetic, biochemical and structural studies indicate that this family contains five separate clades, which exhibit overlapping but distinct substrate specificities created by a process of gene duplication followed by subtle residue divergence within the protease active site. The developmentally regulated expression of these proteases correlates with the passage of the parasite through host tissu... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1880201 Wed, 08 Oct 2008 04:00:00 +0100 1880201 http://www.medworm.com/index.php?rid=1856483&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18835717%26dopt%3DAbstract Authors: Steinmetz MO, Akhmanova A Cytoskeleton-associated protein-glycine-rich (CAP-Gly) domains are protein-interaction modules implicated in important cellular processes and in hereditary human diseases. A prominent function of CAP-Gly domains is to bind to C-terminal EEY/F-COO(-) sequence motifs present in alpha-tubulin and in some microtubule-associated protein tails; however, CAP-Gly domains also interact with other structural elements including end-binding homology domains, zinc-finger motifs and proline-rich sequences. Recent findings unravelled the link between tubulin tyrosination and CAP-Gly-protein recruitment to microtubules. They further provided a molecular basis for understanding the role of CAP-Gly domains in controlling dynamic cellular processes including the trackin... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1856483 Sat, 04 Oct 2008 04:00:00 +0100 1856483 http://www.medworm.com/index.php?rid=1848164&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18829329%26dopt%3DAbstract Authors: Gross A Cells frequently arrest or die in response to DNA damage to reduce the likelihood of progression to malignancy. A recent study sheds new light on the Aven protein, a known apoptotic regulator. After DNA damage, Aven induces cell-cycle arrest via ataxia-telangiectasia-mutated (ATM) kinase activation. These findings add Aven to a growing list of apopototic regulators that function as double agents in the DNA-damage response. PMID: 18829329 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1848164 Mon, 29 Sep 2008 04:00:00 +0100 1848164 http://www.medworm.com/index.php?rid=1837534&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18819805%26dopt%3DAbstract Authors: Smith TJ, Stanley CA Glutamate dehydrogenase (GDH) is found in all living organisms, but only animal GDH is regulated by a large repertoire of metabolites. More than 50 years of research to better understand the mechanism and role of this allosteric network has been frustrated by its sheer complexity. However, recent studies have begun to tease out how and why this complex behavior evolved. Much of GDH regulation probably occurs by controlling a complex ballet of motion necessary for catalytic turnover and has evolved concomitantly with a long antenna-like feature of the structure of the enzyme. Ciliates, the 'missing link' in GDH evolution, might have created the antenna to accommodate changing organelle functions and was refined in humans to, at least in part, link amino aci... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1837534 Wed, 24 Sep 2008 04:00:00 +0100 1837534 http://www.medworm.com/index.php?rid=1833465&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18818085%26dopt%3DAbstract Authors: Eckerdt F, Maller JL Polo-like kinase 1 (Plk1) is essential for checkpoint recovery and the activation of key mitotic enzymes; however, its own activation mechanism has remained elusive. Recent findings show that Bora, a G(2)-M expressed protein, facilitates Plk1 activation by the oncogenic kinase Aurora A in G(2). During mitosis, Plk1-dependent Bora degradation promotes Aurora A localization to the centrosome and/or spindle. Bora-dependent regulation provides important new insights into interactions between key mitotic kinases. PMID: 18818085 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences) Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1833465 Tue, 23 Sep 2008 04:00:00 +0100 1833465 http://www.medworm.com/index.php?rid=1829556&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18815047%26dopt%3DAbstract Authors: Fieldhouse RJ, Merrill AR In the current data-rich era, making the leap from sequence data to knowledge is a task that requires an elegant bioinformatics toolset to pinpoint pressing research questions. Therefore, a strategy to expand important protein-family knowledge is required, particularly in cases in which primary sequence identity is low but structural conservation is high. For example, the mono-ADP-ribosylating toxins fit these criteria and several approaches have been used to accelerate the discovery of new family members. The strategy evolved from conduction of PSI-BLAST searches through to the combination of secondary-structure prediction with pattern-based searches. However, a newly developed tactic, in which fold recognition dominates, reduces reliance on sequence... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1829556 Mon, 22 Sep 2008 04:00:00 +0100 1829556 http://www.medworm.com/index.php?rid=1826263&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18809331%26dopt%3DAbstract Authors: Koh MY, Spivak-Kroizman TR, Powis G The hypoxia-inducible factor-1 (HIF-1) is the master regulator of the cellular response to hypoxia and its expression levels are tightly controlled through synthesis and degradation. It is widely accepted that HIF-1alpha protein accumulation during hypoxia results from inhibition of its oxygen-dependent degradation by the von Hippel Lindau protein (pVHL) pathway. However, recent data describe new pVHL- or oxygen-independent mechanisms for HIF-1alpha degradation. Furthermore, the hypoxia-induced increase in HIF-1alpha levels is facilitated by the continued translation of HIF-1alpha during hypoxia despite the global inhibition of protein translation. Recent work has contributed to an increased understanding of the mechanisms that control the t... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1826263 Sat, 20 Sep 2008 04:00:00 +0100 1826263 http://www.medworm.com/index.php?rid=1815813&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18805010%26dopt%3DAbstract Authors: Kwon HS, Ott M Reversible acetylation has emerged as a key post-translational modification of proteins. Although the number of acetylated proteins is rapidly growing, the ways in which protein acetyltransferases and deacetylases connect with extracellular stimuli remain unclear. Recently, a regulatory network has emerged that controls the expression and activity of SIRT1, a mammalian class-III protein deacetylase. SIRT1 is an important regulator of metabolism, senescence, cancer and, possibly, longevity and is connected with crucial stress-responsive signal-transduction pathways. These connections provide important clues about how protein acetylation and deacetylation mediate cellular adaptations to extrinsic stress. PMID: 18805010 [PubMed - as supplied by publisher] (Sour... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1815813 Thu, 18 Sep 2008 04:00:00 +0100 1815813 http://www.medworm.com/index.php?rid=1798570&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18789696%26dopt%3DAbstract Authors: Holbourn KP, Acharya KR, Perbal B The CCN proteins are key signalling and regulatory molecules involved in many vital biological functions, including cell proliferation, angiogenesis, tumourigenesis and wound healing. How these proteins influence such a range of functions remains incompletely understood but is probably related to their discrete modular nature and a complex array of intra- and inter-molecular interactions with a variety of regulatory proteins and ligands. Although certain aspects of their biology can be attributed to the four individual modules that constitute the CCN proteins, recent results suggest that some of their biological functions require cooperation between modules. Indeed, the modular structure of CCN proteins provides important insight into their st... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1798570 Thu, 11 Sep 2008 04:00:00 +0100 1798570 http://www.medworm.com/index.php?rid=1798569&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18789697%26dopt%3DAbstract Authors: Yona S, Lin HH, Siu WO, Gordon S, Stacey M The G protein-coupled receptor (GPCR) family comprises the largest class of cell surface receptors found in metazoan proteomes. Within the novel GPCR subfamily of adhesion-GPCRs, approximately 150 distinct orthologues, from invertebrates to mammals, have been identified to date. All members of this family contain a large extracellular region, often containing common protein modules, coupled to a seven-transmembrane domain via a stalk region that seems to be crucial for functionality. Owing to their unique structure, restricted expression profile and involvement in several human diseases, adhesion-GPCRs have long been proposed to have vital dual roles in cellular adhesion and signalling. More recent studies have provided structural, ev... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1798569 Wed, 10 Sep 2008 04:00:00 +0100 1798569 http://www.medworm.com/index.php?rid=1790531&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18786828%26dopt%3DAbstract Authors: Schmid M, Jensen TH The diversity of RNAs in the cell continues to amaze. In addition to the 'classic' species of mRNA, tRNA, rRNA, snRNA and snoRNA, it is now clear that the majority of genomic information is transcribed into RNA molecules. The resulting complexity of the transcriptome poses a serious challenge to cells because they must manage numerous RNA-processing reactions, yet, at the same time, eradicate surplus and aberrant material without destroying functional RNA. The 3'-->5' exonucleolytic RNA exosome is emerging as a major facilitator of such events. Recent structural and functional data regarding this fascinating complex and its many co-factors illuminate its diverse biochemical properties and indicate mechanisms by which RNAs are targeted for either processi... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1790531 Tue, 09 Sep 2008 04:00:00 +0100 1790531 http://www.medworm.com/index.php?rid=1782937&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18778941%26dopt%3DAbstract Authors: Anderluh G, Lakey JH Membrane disruption can efficiently alter cellular function; indeed, pore-forming toxins (PFTs) are well known as important bacterial virulence factors. However, recent data have revealed that structures similar to those found in PFTs are found in membrane active proteins across disparate phyla. Many similarities can be identified only at the 3D-structural level. Of note, domains found in membrane-attack complex proteins of complement and perforin (MACPF) resemble cholesterol-dependent cytolysins from Gram-positive bacteria, and the Bcl family of apoptosis regulators share similar architectures with Escherichia coli pore-forming colicins. These and other correlations provide considerable help in understanding the structural requirements for membrane bindin... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1782937 Sat, 06 Sep 2008 04:00:00 +0100 1782937 http://www.medworm.com/index.php?rid=1779734&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18774718%26dopt%3DAbstract Authors: Lecompte O, Poch O, Laporte J Phosphoinositides are lipid second messengers that are essential for many cellular processes, including signal transduction and cell compartmentalization. Among them, phosphatidylinositol 5-phosphate (PtdIns5P) is the least characterized, although several proteins involved in its regulation are implicated in human diseases. We studied the distribution of 32 PtdIns5P-metabolizing proteins in 39 eukaryotic genomes. Phylogenetic profiles identify four groups of co-evolving proteins, confirming known protein complexes and revealing new ones. The complexes comprise a phosphatase, a kinase and a regulator; this indicates that physical interactions between the three partners are necessary for the acute spatial regulation of PtdIns5P turnover. By examinin... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1779734 Fri, 05 Sep 2008 04:00:00 +0100 1779734 http://www.medworm.com/index.php?rid=1779733&cid=s_36134_60_f&fid=36134&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18774719%26dopt%3DAbstract Authors: Chivukula RR, Mendell JT MicroRNAs (miRNAs) have attracted considerable attention because of their important roles in development, normal physiology, and disease states including cancer. Recent studies have identified specific miRNAs that regulate the cell cycle and have documented that the loss or gain of miRNA-mediated cell-cycle control contributes to malignancy. miRNAs regulate classic cell-cycle control pathways by directly targeting proteins such as E2F transcription factors, cyclin-dependent kinases (Cdks), cyclins and Cdk inhibitors. Moreover, from recent findings, it has been suggested that miRNAs themselves might be subject to cell-cycle dependent regulation. Together, these observations indicate that the reciprocal control of RNA silencing and the metazoan cell cycl... Trends in Biochemical Sciences journals http://www.medworm.com/rss/comments.php?id=1779733 Fri, 05 Sep 2008 04:00:00 +0100 1779733