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300 records returned

Mucin-interacting proteins: from function to therapeutics.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 in...
Source: Trends in Biochemical Sciences - November 11, 2009 Category: Biochemistry Authors: Senapati S, Das S, Batra SK Tags: Trends Biochem Sci Source Type: journals

GSK3: a multifaceted kinase in Wnt signaling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 result...
Source: Trends in Biochemical Sciences - October 31, 2009 Category: Biochemistry Authors: Wu D, Pan W Tags: Trends Biochem Sci Source Type: journals

WIP1 phosphatase at the crossroads of cancer and aging.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Trends in Biochemical Sciences - October 28, 2009 Category: Biochemistry Authors: Le Guezennec X, Bulavin DV Tags: Trends Biochem Sci Source Type: journals

TOR complex 2: a signaling pathway of its own.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ge...
Source: Trends in Biochemical Sciences - October 27, 2009 Category: Biochemistry Authors: Cybulski N, Hall MN Tags: Trends Biochem Sci Source Type: journals

Assembly of checkpoint and repair machineries at DNA damage sites.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 detectio...
Source: Trends in Biochemical Sciences - October 27, 2009 Category: Biochemistry Authors: Huen MS, Chen J Tags: Trends Biochem Sci Source Type: journals

Underpinning compartmentalised cAMP signalling through targeted cAMP breakdown.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Trends in Biochemical Sciences - October 26, 2009 Category: Biochemistry Authors: Houslay MD Tags: Trends Biochem Sci Source Type: journals

N-glycan structures: recognition and processing in the ER.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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-c...
Source: Trends in Biochemical Sciences - October 21, 2009 Category: Biochemistry Authors: Aebi M, Bernasconi R, Clerc S, Molinari M Tags: Trends Biochem Sci Source Type: journals

Plasticity of telomere maintenance mechanisms in yeast.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 revea...
Source: Trends in Biochemical Sciences - October 19, 2009 Category: Biochemistry Authors: Lue NF Tags: Trends Biochem Sci Source Type: journals

Observing biological dynamics at atomic resolution using NMR.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 o...
Source: Trends in Biochemical Sciences - October 19, 2009 Category: Biochemistry Authors: Mittermaier AK, Kay LE Tags: Trends Biochem Sci Source Type: journals

Protein-protein interaction networks: how can a hub protein bind so many different partners?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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, protei...
Source: Trends in Biochemical Sciences - October 15, 2009 Category: Biochemistry Authors: Tsai CJ, Ma B, Nussinov R Tags: Trends Biochem Sci Source Type: journals

A G protein-coupled receptor at work: the rhodopsin model.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Trends in Biochemical Sciences - October 14, 2009 Category: Biochemistry Authors: Hofmann KP, Scheerer P, Hildebrand PW, Choe HW, Park JH, Heck M, Ernst OP Tags: Trends Biochem Sci Source Type: journals

Getting down to the phosphorylated 'nuts and bolts' of spindle checkpoint signalling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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, s...
Source: Trends in Biochemical Sciences - October 14, 2009 Category: Biochemistry Authors: Zich J, Hardwick KG Tags: Trends Biochem Sci Source Type: journals

The essential function of HP1beta: a case of the tail wagging the dog?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Trends in Biochemical Sciences - October 14, 2009 Category: Biochemistry Authors: Billur M, Bartunik HD, Singh PB Tags: Trends Biochem Sci Source Type: journals

P2X receptors: dawn of the post-structure era.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Trends in Biochemical Sciences - October 14, 2009 Category: Biochemistry Authors: Young MT Tags: Trends Biochem Sci Source Type: journals

BTG/TOB factors impact deadenylases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 cor...
Source: Trends in Biochemical Sciences - October 11, 2009 Category: Biochemistry Authors: Mauxion F, Chen CY, Séraphin B, Shyu AB Tags: Trends Biochem Sci Source Type: journals

Understanding polyspecificity of multidrug ABC transporters: closing in on the gaps in ABCB1.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 co...
Source: Trends in Biochemical Sciences - October 8, 2009 Category: Biochemistry Authors: Gutmann DA, Ward A, Urbatsch IL, Chang G, van Veen HW Tags: Trends Biochem Sci Source Type: journals

Catalytic and non-catalytic functions of human IIA phospholipase A2.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 a...
Source: Trends in Biochemical Sciences - October 7, 2009 Category: Biochemistry Authors: Birts CN, Barton CH, Wilton DC Tags: Trends Biochem Sci Source Type: journals

Biochemical pathways that regulate acetyltransferase and deacetylase activity in mammalian cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ab...
Source: Trends in Biochemical Sciences - October 7, 2009 Category: Biochemistry Authors: Mellert HS, McMahon SB Tags: Trends Biochem Sci Source Type: journals

Activating immunity: lessons from the TLRs and NLRs.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 provid...
Source: Trends in Biochemical Sciences - October 6, 2009 Category: Biochemistry Authors: Monie TP, Bryant CE, Gay NJ Tags: Trends Biochem Sci Source Type: journals

Lafora disease: insights into neurodegeneration from plant metabolism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Trends in Biochemical Sciences - October 6, 2009 Category: Biochemistry Authors: Gentry MS, Dixon JE, Worby CA Tags: Trends Biochem Sci Source Type: journals

CRL4s: the CUL4-RING E3 ubiquitin ligases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Trends in Biochemical Sciences - October 6, 2009 Category: Biochemistry Authors: Jackson S, Xiong Y Tags: Trends Biochem Sci Source Type: journals

Glutaredoxins: roles in iron homeostasis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ana...
Source: Trends in Biochemical Sciences - October 4, 2009 Category: Biochemistry Authors: Rouhier N, Couturier J, Johnson MK, Jacquot JP Tags: Trends Biochem Sci Source Type: journals

Ras classical effectors: new tales from in silico complexes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Trends in Biochemical Sciences - October 1, 2009 Category: Biochemistry Authors: Fuentes G, Valencia A Tags: Trends Biochem Sci Source Type: journals

Keeping IGF-II under control: Lessons from the IGF-II-IGF2R crystal structure.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 degra...
Source: Trends in Biochemical Sciences - September 28, 2009 Category: Biochemistry Authors: Brown J, Jones EY, Forbes BE Tags: Trends Biochem Sci Source Type: journals

Plasmodium falciparum neutral aminopeptidases: new targets for anti-malarials.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 an...
Source: Trends in Biochemical Sciences - September 28, 2009 Category: Biochemistry 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 Tags: Trends Biochem Sci Source Type: journals

Mammalian two-hybrids come of age.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Trends in Biochemical Sciences - September 25, 2009 Category: Biochemistry Authors: Lievens S, Lemmens I, Tavernier J Tags: Trends Biochem Sci Source Type: journals

Darwin, natural selection and the biological essentiality of aluminium and silicon.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 myri...
Source: Trends in Biochemical Sciences - September 18, 2009 Category: Biochemistry Authors: Exley C Tags: Trends Biochem Sci Source Type: journals

ABC transporters: a riddle wrapped in a mystery inside an enigma.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 cytos...
Source: Trends in Biochemical Sciences - September 10, 2009 Category: Biochemistry Authors: Jones PM, O'Mara ML, George AM Tags: Trends Biochem Sci Source Type: journals

Cell regulation: determined to signal discrete cooperation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Trends in Biochemical Sciences - September 7, 2009 Category: Biochemistry Authors: Gibson TJ Tags: Trends Biochem Sci Source Type: journals

Post-translational modifications in circadian rhythms.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 relate...
Source: Trends in Biochemical Sciences - September 6, 2009 Category: Biochemistry Authors: Mehra A, Baker CL, Loros JJ, Dunlap JC Tags: Trends Biochem Sci Source Type: journals

Stem cells, stress, metabolism and cancer: a drama in two Octs.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 pheno...
Source: Trends in Biochemical Sciences - September 2, 2009 Category: Biochemistry Authors: Kang J, Shakya A, Tantin D Tags: Trends Biochem Sci Source Type: journals

Obituary: Ephraim Katchalski-Katzir (1916-2009).Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19733081 [PubMed - as supplied by publisher] (Source: Trends in Biochemical Sciences)
Source: Trends in Biochemical Sciences - September 1, 2009 Category: Biochemistry Authors: Eisenbach M Tags: Trends Biochem Sci Source Type: journals

Focus on the splicing of Secretin GPCRs transmembrane-domain 7.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 con...
Source: Trends in Biochemical Sciences - September 1, 2009 Category: Biochemistry Authors: Markovic D, Grammatopoulos DK Tags: Trends Biochem Sci Source Type: journals

Heparanase: busy at the cell surface.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 m...
Source: Trends in Biochemical Sciences - September 1, 2009 Category: Biochemistry Authors: Fux L, Ilan N, Sanderson RD, Vlodavsky I Tags: Trends Biochem Sci Source Type: journals

Adipokines as novel modulators of lipid metabolism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 pathoph...
Source: Trends in Biochemical Sciences - August 31, 2009 Category: Biochemistry Authors: Lago F, Gómez R, Gómez-Reino JJ, Dieguez C, Gualillo O Tags: Trends Biochem Sci Source Type: journals

When DNA replication and protein synthesis come together.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 su...
Source: Trends in Biochemical Sciences - August 31, 2009 Category: Biochemistry Authors: Berthon J, Fujikane R, Forterre P Tags: Trends Biochem Sci Source Type: journals

Re-capping the message.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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. The...
Source: Trends in Biochemical Sciences - August 31, 2009 Category: Biochemistry Authors: Schoenberg DR, Maquat LE Tags: Trends Biochem Sci Source Type: journals

The emerging roles of serine protease cascades in the epidermis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 associat...
Source: Trends in Biochemical Sciences - August 30, 2009 Category: Biochemistry Authors: Ovaere P, Lippens S, Vandenabeele P, Declercq W Tags: Trends Biochem Sci Source Type: journals

The cost of DNA bending.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 rigi...
Source: Trends in Biochemical Sciences - August 30, 2009 Category: Biochemistry Authors: Privalov PL, Dragan AI, Crane-Robinson C Tags: Trends Biochem Sci Source Type: journals

Amyloids in bacterial inclusion bodies.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 u...
Source: Trends in Biochemical Sciences - July 29, 2009 Category: Biochemistry Authors: de Groot NS, Sabate R, Ventura S Tags: Trends Biochem Sci Source Type: journals

Navigating the ribosome's metastable energy landscape.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ensem...
Source: Trends in Biochemical Sciences - July 29, 2009 Category: Biochemistry Authors: Munro JB, Sanbonmatsu KY, Spahn CM, Blanchard SC Tags: Trends Biochem Sci Source Type: journals

Cotranslational processing mechanisms: towards a dynamic 3D model.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ope...
Source: Trends in Biochemical Sciences - July 29, 2009 Category: Biochemistry Authors: Giglione C, Fieulaine S, Meinnel T Tags: Trends Biochem Sci Source Type: journals

Evolution of the haem copper oxidases superfamily: a rooting tale.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 c...
Source: Trends in Biochemical Sciences - July 29, 2009 Category: Biochemistry Authors: Gribaldo S, Talla E, Brochier-Armanet C Tags: Trends Biochem Sci Source Type: journals

The published 3D structure of the VDAC channel: native or not?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 disc...
Source: Trends in Biochemical Sciences - July 29, 2009 Category: Biochemistry Authors: Colombini M Tags: Trends Biochem Sci Source Type: journals

CRISPR-based adaptive and heritable immunity in prokaryotes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 C...
Source: Trends in Biochemical Sciences - July 28, 2009 Category: Biochemistry Authors: van der Oost J, Jore MM, Westra ER, Lundgren M, Brouns SJ Tags: Trends Biochem Sci Source Type: journals

Mitochondrial DNA replication and repair: all a flap.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 o...
Source: Trends in Biochemical Sciences - June 23, 2009 Category: Biochemistry Authors: Holt IJ Tags: Trends Biochem Sci Source Type: journals

IF(1): setting the pace of the F(1)F(o)-ATP synthase.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 researc...
Source: Trends in Biochemical Sciences - June 23, 2009 Category: Biochemistry Authors: Campanella M, Parker N, Tan CH, Hall AM, Duchen MR Tags: Trends Biochem Sci Source Type: journals

The tau of MARK: a polarized view of the cytoskeleton.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Trends in Biochemical Sciences - June 23, 2009 Category: Biochemistry Authors: Matenia D, Mandelkow EM Tags: Trends Biochem Sci Source Type: journals

SitePredicting the cleavage of proteinase substrates.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 liter...
Source: Trends in Biochemical Sciences - June 19, 2009 Category: Biochemistry Authors: Verspurten J, Gevaert K, Declercq W, Vandenabeele P Tags: Trends Biochem Sci Source Type: journals

Coordinating cellular events during spermatogenesis: a biochemical model.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Trends in Biochemical Sciences - June 14, 2009 Category: Biochemistry Authors: Lie PP, Cheng CY, Mruk DD Tags: Trends Biochem Sci Source Type: journals