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Rho GTPase function in tumorigenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Malignant tumor cells display uncontrolled proliferation, loss of epithelial cell polarity, altered interactions with neighboring cells and the surrounding extracellular matrix, and enhanced migratory properties. Proteins of the Rho GTPase family regulate all these processes in cell culture and, for that reason, Rho GTPases, their regulators, and their effectors have been suggested to control tumor formation and progression in humans. However, while the tumor-relevant functions of Rho GTPases are very well documented in vitro, we are only now beginning to assess their contribution to cancer in human patients and in ani...
Source: Biochimica et Biophysica Acta - November 7, 2009 Category: Biochemistry Authors: Karlsson R, Pedersen ED, Wang Z, Brakebusch C Tags: Biochim Biophys Acta Source Type: journals

The RASSF proteins in cancer; from epigenetic silencing to functional characterization.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The Ras-Association Domain Family (RASSF) comprises ten members, termed RASSF1 to RASSF10. RASSF1 to RASSF6 harbor a C-terminal Ras-association (RA) domain and RASSF7 to RASSF10 contain an N-terminal RA domain. Interestingly, it was observed that in various tumor types distinct RASSFs transcripts (e.g. RASSF1A and RASSF2A) are missing due to hypermethylation of their CpG island promoter. Since methylation of the RASSF1A promoter is described as an early and frequent event in tumorigenesis, RASSF1A could serve as a useful diagnostic marker in cancer screens. RASSFs are implicated in various cellular mechanisms including...
Source: Biochimica et Biophysica Acta - November 7, 2009 Category: Biochemistry Authors: Richter AM, Pfeifer GP, Dammann RH Tags: Biochim Biophys Acta Source Type: journals

Translocations in epithelial cancers.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Genomic translocations leading to the expression of chimeric transcripts characterize several hematologic, mesenchymal and epithelial malignancies. While several gene fusions have been linked to essential molecular events in hematologic malignancies, the identification and characterization of recurrent chimeric transcripts in epithelial cancers has been limited. However, the recent discovery of the recurrent gene fusions in prostate cancer has sparked a revitalization of the quest to identify novel rearrangements in epithelial malignancies. Here, the molecular mechanisms of gene fusions that drive several epithelial ca...
Source: Biochimica et Biophysica Acta - November 7, 2009 Category: Biochemistry Authors: Brenner JC, Chinnaiyan AM Tags: Biochim Biophys Acta Source Type: journals

Genomic and proteomic biomarkers for cancer: a multitude of opportunities.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biomarkers are molecular indicators of a biological status, and as biochemical species can be assayed to evaluate the presence of cancer and therapeutic interventions. Through a variety of mechanisms cancer cells provide the biomarker material for their own detection. Biomarkers may be detectable in the blood, other body fluids, or tissues. The expectation is that the level of an informative biomarker is related to the specific type of disease present in the body. Biomarkers have potential both as diagnostic indicators and monitors of the effectiveness of clinical interventions. Biomarkers are also able to stratify can...
Source: Biochimica et Biophysica Acta - November 7, 2009 Category: Biochemistry Authors: Tainsky MA Tags: Biochim Biophys Acta Source Type: journals

The role of mammalian ribonucleases (RNases) in cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Ribonucleases (RNases) are a group of enzymes that cleave RNAs at phosphodiester bonds resulting in remarkably diverse biological consequences. This review focuses on mammalian RNases that are capable of, or potentially capable of, cleaving messenger RNA (mRNA) as well as other RNAs in cells and play roles in the development of human cancers. The aims of this review are to provide an overview of the roles of currently known mammalian RNases, and the evidence that associate them as regulators of tumor development. The roles of these RNases as oncoproteins and/or tumor suppressors in influencing cell growth, apoptosis, a...
Source: Biochimica et Biophysica Acta - November 7, 2009 Category: Biochemistry Authors: Kim WC, Lee CH Tags: Biochim Biophys Acta Source Type: journals

Sorting out the functional role(s) of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) in cell proliferation and cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) has many beneficial physiological functions ranging from enhancing fatty acid catabolism, improving insulin sensitivity, inhibiting inflammation and increasing oxidative myofibers allowing for improved athletic performance. Thus, given the potential for targeting PPARbeta/delta for the prevention and/or treatment of diseases including diabetes, dyslipidemias, metabolic syndrome and cancer, it is critical to clarify the functional role of PPARbeta/delta in cell proliferation and associated disorders such as cancer. However, there is considerable cont...
Source: Biochimica et Biophysica Acta - November 7, 2009 Category: Biochemistry Authors: Peters JM, Gonzalez FJ Tags: Biochim Biophys Acta Source Type: journals

A systems biology view of cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In order to understand how a cancer cell is functionally different from a normal cell it is necessary to assess the complex network of pathways involving gene regulation, signaling, and cell metabolism, and the alterations in its dynamics caused by the several different types of mutations leading to malignancy. Since the network is typically complex, with multiple connections between pathways and important feedback loops, it is crucial to represent it in the form of a computational model that can be used for a rigorous analysis. This is the approach of systems biology, made possible by new -omics data generation techno...
Source: Biochimica et Biophysica Acta - November 7, 2009 Category: Biochemistry Authors: Laubenbacher R, Hower V, Jarrah A, Torti SV, Shulaev V, Mendes P, Torti FM, Akman S Tags: Biochim Biophys Acta Source Type: journals

ERalpha-negative and triple negative breast cancer: molecular features and potential therapeutic approaches.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Triple negative breast cancer (TNBC) is a type of aggressive breast cancer lacking the expression of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor-2 (HER-2). TNBC patients account for approximately 15% of total breast cancer patients and are more prevalent among young African, African-American and Latino women patients. The currently available ER-targeted and Her-2-based therapies are not effective for treating TNBC. Recent studies have revealed a number of novel features of TNBC. In the present work, we comprehensively addressed these features and discussed potential t...
Source: Biochimica et Biophysica Acta - November 7, 2009 Category: Biochemistry Authors: Chen JQ, Russo J Tags: Biochim Biophys Acta Source Type: journals

Estrogens, MSI and Lynch syndrome-associated tumors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Estrogens play a major role in the biology of hormone-responsive tissues but also in the normal physiology of various non-typical hormone-responsive tissues. In disease, estrogens have been associated with tumor development, in particular with tumors such as breast, endometrium, ovary and prostate. In this paper we will review the molecular mechanisms by which estrogens are involved in cancer development, with a special focus in Lynch syndrome related neoplasia. Further, we discuss the role estrogens might have on cell proliferation and apoptosis, how estrogens metabolites can induce DNA damage and we discuss a possibl...
Source: Biochimica et Biophysica Acta - November 7, 2009 Category: Biochemistry Authors: Ferreira AM, Westers H, Albergaria A, Seruca R, Hofstra RM Tags: Biochim Biophys Acta Source Type: journals

Tumor cell energy metabolism and its common features with yeast metabolism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
During the last decades a considerable amount of research has been focused on cancer. A number of genetic and signaling defects have been identified. This has allowed the design and screening of a number of anti-tumor drugs for therapeutic use. One of the main challenges of anti-cancer therapy is to specifically target these drugs to malignant cells. Recently, tumor cell metabolism has been considered as a possible target for cancer therapy. It is widely accepted that tumors display an enhanced glycolytic activity and oxidative phosphorylation down-regulation (Warburg effect). Therefore, it seems reasonable that disrup...
Source: Biochimica et Biophysica Acta - November 7, 2009 Category: Biochemistry Authors: Diaz-Ruiz R, Uribe-Carvajal S, Devin A, Rigoulet M Tags: Biochim Biophys Acta Source Type: journals

Roles of P67/MetAP2 as a tumor suppressor.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A precise balance between growth promoting signals and growth inhibitory signals plays important roles in the maintenance of healthy mammalian cells. Any deregulation of this critical balance converts normal cells into abnormal or cancerous cells. Several macromolecules are being identified and characterized that are involved in the regulation of cell signaling pathways that connect to the cell cycle and thus they play roles as tumor promoters or tumor suppressors. In situ tumor formation needs active angiogenesis, a process that generates new blood vessels from existing ones either by splitting or sprouting. Several s...
Source: Biochimica et Biophysica Acta - November 7, 2009 Category: Biochemistry Authors: Datta B Tags: Biochim Biophys Acta Source Type: journals

Measurements of mitochondrial calcium in vivo.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mitochondria play a pivotal role in intracellular Ca(2+) signalling by taking up and releasing the ion upon specific conditions. In order to do so, mitochondria depend on a number of factors, such as the mitochondrial membrane potential and spatio-temporal constraints. Whereas most of the basic principles underlying mitochondrial Ca(2+) handling have been successfully deciphered over the last 50 years using assays based on in vitro preparations of mitochondria or cultured cells, we have only just started to understand the actual physiological relevance of these processes in the whole animal. Recent advancements in imag...
Source: Biochimica et Biophysica Acta - October 25, 2009 Category: Biochemistry Authors: Pozzan T, Rudolf R Tags: Biochim Biophys Acta Source Type: journals

Calcium regulation of mitochondria motility and morphology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In the Fifties, electron microscopy studies on neuronal cells showed that mitochondria typically cluster at synaptic terminals, thereby introducing the concept that proper mitochondria trafficking and partitioning inside the cell could provide functional support to the execution of key physiological processes. Today, the notion that a central event in the life of every eukaryotic cell is to configure, maintain, and reorganize the mitochondrial network at sites of high energy demand in response to environmental and cellular cues is well established, and the challenge ahead is to define the underlying molecular mechanism...
Source: Biochimica et Biophysica Acta - October 25, 2009 Category: Biochemistry Authors: Jeyaraju DV, Cisbani G, Pellegrini L Tags: Biochim Biophys Acta Source Type: journals

The role of the mitochondrial permeability transition pore in heart disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Like Dr. Jeckyll and Mr. Hyde, mitochondria possess two distinct persona. Under normal physiological conditions they synthesise ATP to meet the energy needs of the beating heart. Here calcium acts as a signal to balance the rate of ATP production with ATP demand. However, when the heart is overloaded with calcium, especially when this is accompanied by oxidative stress, mitochondria embrace their darker side, and induce necrotic cell death of the myocytes. This happens acutely in reperfusion injury and chronically in congestive heart failure. Here calcium overload, adenine nucleotide depletion and oxidative stress comb...
Source: Biochimica et Biophysica Acta - October 25, 2009 Category: Biochemistry Authors: Halestrap AP, Pasdois P Tags: Biochim Biophys Acta Source Type: journals

Ca(2+) transfer from the ER to mitochondria: when, how and why.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The heterogenous subcellular distribution of a wide array of channels, pumps and exchangers allows extracellular stimuli to induce increases in cytoplasmic Ca(2+) concentration ([Ca(2+)]c) with highly defined spatial and temporal patterns, that in turn induce specific cellular responses (e.g. contraction, secretion, proliferation or cell death). In this extreme complexity, the role of mitochondria was considered marginal, till the direct measurement with targeted indicators allowed to appreciate that rapid and large increases of the [Ca(2+)] in the mitochondrial matrix ([Ca(2+)]m) invariably follow the cytosolic rises....
Source: Biochimica et Biophysica Acta - October 25, 2009 Category: Biochemistry Authors: Rizzuto R, Marchi S, Bonora M, Aguiari P, Bononi A, De Stefani D, Giorgi C, Leo S, Rimessi A, Siviero R, Zecchini E, Pinton P Tags: Biochim Biophys Acta Source Type: journals

Modulation of calcium signalling by mitochondria.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this review we will attempt to summarise the complex and sometimes contradictory effects that mitochondria have on different forms of calcium signalling. Mitochondria can influence Ca(2+) signalling indirectly by changing the concentration of ATP, NAD(P)H, pyruvate and reactive oxygen species - which in turn modulate components of the Ca(2+) signalling machinery i.e. buffering, release from internal stores, influx from the extracellular solution, uptake into cellular organelles and extrusion by plasma membrane Ca(2+) pumps. Mitochondria can directly influence the calcium concentration in the cytosol of the cell by i...
Source: Biochimica et Biophysica Acta - October 25, 2009 Category: Biochemistry Authors: Walsh C, Barrow S, Voronina S, Chvanov M, Petersen OH, Tepikin A Tags: Biochim Biophys Acta Source Type: journals

Mitochondrial calcium as a key regulator of mitochondrial ATP production in mammalian cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mitochondrial Ca(2+) transport was initially considered important only in buffering of cytosolic Ca(2+) by acting as a "sink" under conditions of Ca(2+) overload. The main regulator of ATP production was considered to be the relative concentrations of high energy phosphates. However, work by Denton and McCormack in the 1970s and 1980s showed that free intramitochondrial Ca(2+) ([Ca(2+)](m)) activated dehydrogenase enzymes in mitochondria, leading to increased NADH and hence ATP production. This leads them to propose a scheme, subsequently termed a "parallel activation model" whereby increases in energy demand, such as ...
Source: Biochimica et Biophysica Acta - October 25, 2009 Category: Biochemistry Authors: Griffiths EJ, Rutter GA Tags: Biochim Biophys Acta Source Type: journals

Regulation of mitochondrial dehydrogenases by calcium ions.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Studies in Bristol in the 1960s and 1970s, led to the recognition that four mitochondrial dehydrogenases are activated by calcium ions. These are FAD-glycerol phosphate dehydrogenase, pyruvate dehydrogenase, NAD-isocitrate dehydrogenase and oxoglutarate dehydrogenase. FAD-glycerol phosphate dehydrogenase is located on the outer surface of the inner mitochondrial membrane and is influenced by changes in cytoplasmic calcium ion concentration. The other three enzymes are located within mitochondria and are regulated by changes in mitochondrial matrix calcium ion concentration. These and subsequent studies on purified enzy...
Source: Biochimica et Biophysica Acta - October 25, 2009 Category: Biochemistry Authors: Denton RM Tags: Biochim Biophys Acta Source Type: journals

The role of Ca(2+) signaling in the coordination of mitochondrial ATP production with cardiac work.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The heart is capable of balancing the rate of mitochondrial ATP production with utilization continuously over a wide range of activity. This results in a constant phosphorylation potential despite a large change in metabolite turnover. The molecular mechanisms responsible for generating this energy homeostasis are poorly understood. The best candidate for a cytosolic signaling molecule reflecting ATP hydrolysis is Ca(2+). Since Ca(2+) initiates and powers muscle contraction as well as serves as the primary substrate for SERCA, Ca(2+) is an ideal feed-forward signal for priming ATP production. With the sarcoplasmic reti...
Source: Biochimica et Biophysica Acta - October 25, 2009 Category: Biochemistry Authors: Balaban RS Tags: Biochim Biophys Acta Source Type: journals

Quercetin can act either as an inhibitor or an inducer of the mitochondrial permeability transition pore: A demonstration of the ambivalent redox character of polyphenols.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The Ca(2+)- and oxidative stress-induced mitochondrial permeability transition (MPT) plays an important role in phenomena ranging from tissue damage upon infarction to muscle wasting in some forms of dystrophy. The process is due to the activation of a large pore in the inner mitochondrial membrane. Anti-oxidants are considered a preventive and remedial tool, and mitochondria-targeted redox-active compounds have been developed. Plant polyphenols are generally considered as anti-oxidants, and thus candidates to the role of mitochondria-protecting agents. In patch-clamp experiments, easily oxidizable polyphenols induced ...
Source: Biochimica et Biophysica Acta - October 25, 2009 Category: Biochemistry Authors: De Marchi U, Biasutto L, Garbisa S, Toninello A, Zoratti M Tags: Biochim Biophys Acta Source Type: journals

Hypoxia and the metabolic phenotype of prostate cancer cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Many cancer cells have an unusual ability to grow in hypoxia, but the origins of this metabolic phenotype remain unclear. We compared the metabolic phenotypes of three common prostate cancer cell models (LNCaP, DU145, PC3), assessing energy metabolism, metabolic gene expression, and the response to various culture contexts (in vitro and xenografts). LNCaP cells had a more oxidative phenotype than PC3 and DU145 cells based upon respiration, lactate production, [ATP], metabolic gene expression, and sensitivity of these parameters to hypoxia. PC3 and DU145 cells possessed similar Complex II and mtDNA levels, but lower Com...
Source: Biochimica et Biophysica Acta - October 25, 2009 Category: Biochemistry Authors: Higgins LH, Withers HG, Garbens A, Love HD, Magnoni L, Hayward SW, Moyes CD Tags: Biochim Biophys Acta Source Type: journals

SR/ER-mitochondrial local communication: calcium and ROS.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We describe here possible mechanisms of the mutual interaction between local Ca(2+) and ROS signaling in the control of SR/ER-mitochondrial function. PMID: 19527680 [PubMed - indexed for MEDLINE] (Source: Biochimica et Biophysica Acta)
Source: Biochimica et Biophysica Acta - October 25, 2009 Category: Biochemistry Authors: Csordás G, Hajnóczky G Tags: Biochim Biophys Acta Source Type: journals

Dysregulation of glucose homeostasis in nicotinamide nucleotide transhydrogenase knockout mice is independent of uncoupling protein 2.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Glucose intolerance in C57Bl/6 mice has been associated with mutations in the nicotinamide nucleotide transhydrogenase (Nnt) gene. It has been proposed that the absence of NNT from mitochondria leads to increased mitochondrial reactive oxygen species production and subsequent activation of uncoupling protein 2 (UCP2). Activation of UCP2 has been suggested to uncouple electron transport from ATP synthesis in pancreatic beta cell mitochondria thereby decreasing glucose tolerance due to decreased insulin secretion through lower ATP/ADP ratios. The hypothesis tested in this paper is that UCP2 function is required for the d...
Source: Biochimica et Biophysica Acta - October 25, 2009 Category: Biochemistry Authors: Parker N, Vidal-Puig AJ, Azzu V, Brand MD Tags: Biochim Biophys Acta Source Type: journals

Differential requirement of two homologous proteins encoded by sll1214 and sll1874 for the reaction of Mg protoporphyrin monomethylester oxidative cyclase under aerobic and micro-oxic growth conditions.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The two open reading frames in the Synechocystis sp. PCC 6803 genome, sll1214 and sll1874, here designated cycI and cycII, respectively, encode similar proteins, which are involved in the Mg protoporphyrin monomethylester (MgProtoME) cyclase reaction. The impairment of tetrapyrrole biosynthesis was examined by separate inactivation of both cyclase encoding genes followed by analysis of chlorophyll contents, MgProtoME levels and several enzyme activities of tetrapyrrole biosynthesis. We additionally addressed the question, whether the two isoforms can complement cyclase deficiency under normal aerobic and micro-oxic gro...
Source: Biochimica et Biophysica Acta - October 25, 2009 Category: Biochemistry Authors: Peter E, Salinas A, Wallner T, Jeske D, Dienst D, Wilde A, Grimm B Tags: Biochim Biophys Acta Source Type: journals

Export or recombination of charges in reaction centers in intact cells of photosynthetic bacteria.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The kinetics and thermodynamics of forward and reverse electron transfer around the reaction center of purple bacterium Rhodobacter sphaeroides were studied in vivo by flash-excited delayed fluorescence, prompt fluorescence (induction) and kinetic difference absorption. By protection of the photomultiplier from intense bacteriochlorophyll prompt fluorescence evoked by laser excitation, the time resolution of the fluorometer was reduced typically 10 micros. Two precursor states of the delayed fluorescence were identified: P(+)Q(A)(-) and cyt c(2)(3+)Q(A)(-) whose enthalpy levels were 340 meV and 1020 meV below A, respec...
Source: Biochimica et Biophysica Acta - October 25, 2009 Category: Biochemistry Authors: Asztalos E, Maróti P Tags: Biochim Biophys Acta Source Type: journals

Localization of cytochrome b6f complexes implies an incomplete respiratory chain in cytoplasmic membranes of the cyanobacterium Synechocystis sp. PCC 6803.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study deletion mutants of all three petC genes of Synechocystis sp. PCC 6803 were constructed to investigate their localization, involvement in electron transfer, respiration and photohydrogen evolution. Immunoblots revealed that PetC1, PetC2, and all other core subunits were exclusively localized in the thylakoids, while the third Rieske protein (PetC3) was the only subunit found in the cytoplasmic membrane. Deletion of petC3 and both of the quinol oxidases failed to elicit a change in respiration rate, when compared to the respective oxidase mutant. This supports a different function of PetC3 other than respirato...
Source: Biochimica et Biophysica Acta - October 25, 2009 Category: Biochemistry Authors: Schultze M, Forberich B, Rexroth S, Dyczmons NG, Roegner M, Appel J Tags: Biochim Biophys Acta Source Type: journals

Ca2+-induced permeability transition can be observed even in yeast mitochondria under optimized experimental conditions.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we examined in detail the effects of Ca(2+) on yeast mitochondria under various conditions. As a result, we discovered that the PT could be induced even in yeast mitochondria by externally added Ca(2+) under optimized experimental conditions. The 2 essential parameters for proper observation of the PT-inducing effects of Ca(2+) were the concentrations of the respiratory substrate and that of inorganic phosphate (Pi) in the incubation medium. The yeast mitochondrial PT induced by Ca(2+) was found to be insensitive to cyclosporin A and suppressed in the presence of a high concentration of Pi. Furthermore, when...
Source: Biochimica et Biophysica Acta - October 25, 2009 Category: Biochemistry Authors: Yamada A, Yamamoto T, Yoshimura Y, Gouda S, Kawashima S, Yamazaki N, Yamashita K, Kataoka M, Nagata T, Terada H, Pfeiffer DR, Shinohara Y Tags: Biochim Biophys Acta Source Type: journals

Special issue on selenoprotein expression and function.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19835757 [PubMed - in process] (Source: Biochimica et Biophysica Acta)
Source: Biochimica et Biophysica Acta - October 21, 2009 Category: Biochemistry Authors: Lillig CH, Arnér E Tags: Biochim Biophys Acta Source Type: journals

Mitochondrial calcium in health and disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19695375 [PubMed - in process] (Source: Biochimica et Biophysica Acta)
Source: Biochimica et Biophysica Acta - August 23, 2009 Category: Biochemistry Authors: Halestrap AP Tags: Biochim Biophys Acta Source Type: journals

Epigenetic control of gene expression.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19683099 [PubMed - in process] (Source: Biochimica et Biophysica Acta)
Source: Biochimica et Biophysica Acta - August 19, 2009 Category: Biochemistry Authors: Ekström TJ Tags: Biochim Biophys Acta Source Type: journals

Association of the herpes simplex virus major tegument structural protein VP22 with chromatin.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The abundant tegument protein VP22 has homologs throughout the alphaherpesvirus family. Numerous groups have been involved in the examination of these homologs, trying to decipher their multiple functions. Investigations early on indicated that VP22 associates with chromatin and further evidence has accumulated in recent years, correlating this protein with chromatin and its components. Ongoing and future studies will determine whether this association with chromatin is specific and whether it serves a function during infection in a physiologically relevant setting. PMID: 19682615 [PubMed - as supplied by publisher...
Source: Biochimica et Biophysica Acta - August 12, 2009 Category: Biochemistry Authors: Ingvarsdottir K, Blaho JA Tags: Biochim Biophys Acta Source Type: journals

Trop2: A possible therapeutic target for late stage epithelial carcinomas.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Trop2 is a cell surface glycoprotein overexpressed in a variety of late stage epithelial carcinomas with low to no expression in normal tissues. Some of the important roles that Trop2 plays in epithelial cancers have recently been revealed. Trop2 overexpression is associated with decreased patient survival as well as increased tumor aggressiveness and metastasis. Its high overexpression in metastatic tissue makes it a very attractive and potential therapeutic target for late stage disease. This protein can transduce an intracellular calcium signal and contains a conserved phosphatidylinositol 4,5-bisphosphate (PIP(2)) ...
Source: Biochimica et Biophysica Acta - August 12, 2009 Category: Biochemistry Authors: Cubas R, Li M, Chen C, Yao Q Tags: Biochim Biophys Acta Source Type: journals

Metastasis mechanisms.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Metastasis, the spread of malignant cells from a primary tumor to distant sites, poses the biggest problem to cancer treatment and is the main cause of death of cancer patients. It occurs in a series of discrete steps, which have been modeled into a "metastatic cascade". In this review, we comprehensively describe the molecular and cellular mechanisms underlying the different steps, including Epithelial-Mesenchymal Transition (EMT), invasion, anoikis, angiogenesis, transport through vessels and outgrowth of secondary tumors. Furthermore, we implement recent findings that have broadened and challenged the classical view...
Source: Biochimica et Biophysica Acta - August 12, 2009 Category: Biochemistry Authors: Geiger TR, Peeper DS Tags: Biochim Biophys Acta Source Type: journals

Downstream mechanisms triggered by mitochondrial dysfunction in the basal ganglia: From experimental models to neurodegenerative diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mitochondrial dysfunctions have been implicated in the cellular processes underlying several neurodegenerative disorders affecting the basal ganglia. These include Huntington's chorea and Parkinson's disease, two highly debilitating motor disorders for which recent research has also involved gene mutation linked to mitochondrial deficits. Experimental models of basal ganglia diseases have been developed by using toxins able to disrupt mitochondrial function: these molecules act by selectively inhibiting mitochondrial respiratory complexes, uncoupling cellular respiration. This in turn leads to oxidative stress and ener...
Source: Biochimica et Biophysica Acta - August 12, 2009 Category: Biochemistry Authors: Gubellini P, Picconi B, Di Filippo M, Calabresi P Tags: Biochim Biophys Acta Source Type: journals

Fluorescence studies on the interaction of choline-binding domain B of the major bovine seminal plasma protein, PDC-109 with phospholipid membranes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The microenvironment and accessibility of the tryptophan residues in domain B of PDC-109 (PDC-109/B) in the native state and upon ligand binding have been investigated by fluorescence quenching, time resolved fluorescence and red-edge excitation shift (REES) studies. The increase in the intrinsic fluorescence emission intensity of PDC-109/B upon binding to lysophosphatodylcholine (Lyso-PC) micelles and dimyristoylphosphatidylcholine (DMPC) membranes was considerably less as compared to that observed with the whole PDC-109 protein. The degree of quenching achieved by different quenchers with PDC-109/B bound to Lyso-PC a...
Source: Biochimica et Biophysica Acta - August 12, 2009 Category: Biochemistry Authors: Damai RS, Anbazhagan V, Rao KB, Swamy MJ Tags: Biochim Biophys Acta Source Type: journals

Domain-specific determinants of catalysis/ substrate binding and the oligomerization status of barley UDP-glucose pyrophosphorylase.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, several barley UGPase mutants were produced, either single amino acid mutants or involving deletions of N- and C-terminal domains (Ncut and Ccut mutants, respectively) and of active site region ("NB loop"). The Del-NB mutant yielded no activity, whereas Ncut deletions and most of Ccut mutants, including short deletions at the so called "I-loop" region of C-terminal domain, as well as a single K260A mutant resulted in very low activity. For wt and the mutants, kinetics with UDPG were linear on reciprocal plots, whereas PPi at concentrations above 1 mM exerted strong substrate inhibition. Both K260A and most o...
Source: Biochimica et Biophysica Acta - August 12, 2009 Category: Biochemistry Authors: Meng M, Fitzek E, Gajowniczek A, Wilczynska M, Kleczkowski LA Tags: Biochim Biophys Acta Source Type: journals

Ion beam radiobiology and cancer: Time to update ourselves.Email this article to a colleague. Save this article to My Clippings. discuss this article 1 CommentDiscuss or comment on this article.
High-energy protons and carbon ions exhibit an inverse dose profile allowing for increased energy deposition with penetration depth. Additionally, heavier ions like carbon beams have the advantage of a markedly increased biological effectiveness characterized by enhanced ionization density in the individual tracks of the heavy particles, where DNA damage becomes clustered and therefore more difficult to repair, but is restricted to the end of their range. These superior biophysical and biological profiles of particle beams over conventional radiotherapy permit more precise dose localization and make them highly attract...
Source: Biochimica et Biophysica Acta - August 11, 2009 Category: Biochemistry Authors: Fokas E, Kraft G, An H, Engenhart-Cabillic R Tags: Biochim Biophys Acta Source Type: journals

Chromatin assembly on herpes simplex virus genomes during lytic infection.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The human herpes simplex viruses HSV-1 and HSV-2 infect a significant portion of the human population. Both viruses can undergo lytic infection in epithelial cells and establish lifelong latency in neuronal cells. The large HSV-1 DNA genomes have long been considered to be devoid of histones both inside the virion particle and inside the cell during lytic infection, but to be packaged in repressive chromatin during latency. However, recent reports indicate that many histone and non-histone chromosomal proteins can associate with viral DNA during lytic infection and may influence important events during the HSV-1 lytic ...
Source: Biochimica et Biophysica Acta - August 11, 2009 Category: Biochemistry Authors: Lu X, Triezenberg SJ Tags: Biochim Biophys Acta Source Type: journals

Kinetic characterization of human phosphopantothenoylcysteine synthetase.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Phosphopantothenoylcysteine synthetase (PPCS) catalyzes the formation of phosphopantothenoylcysteine from (R)-phosphopantothenate and l-cysteine with the concomitant consumption of a nucleotide triphosphate. Herein, the human coaB gene encoding PPCS is cloned into pET23a and overexpressed in E. coli BL21(DE3), to yield 10mg of purified enzyme per liter of culture. Detailed kinetic studies found that this PPCS follows a similar Bi Uni Uni Bi Ping Pong mechanism as previously described for the E. faecalis PPCS, except that the human enzyme can use both ATP and CTP with similar affinity. One significant difference for hum...
Source: Biochimica et Biophysica Acta - August 11, 2009 Category: Biochemistry Authors: Yao J, Dotson GD Tags: Biochim Biophys Acta Source Type: journals

Kinetics and thermodynamics of the interaction of 1-anilino-naphtalene-8-sulfonate with proteins.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Despite 1-anilino-naphtalene-8-sulfonate (ANS) has been widely used in protein folding studies and binding, the detailed mechanism of this interaction is not fully understood. In this work the binding of ANS was analyzed at pre-equilibrium and equilibrium conditions using bovine serum albumin (BSA) as a model. We employed a combined approach including the analysis of fluorescence, near-UV circular dichroism and isothermal titration calorimetric data. Experiments at equilibrium with these techniques identify three ANS molecules bound at hydrophobic cavities in BSA. Pre-equilibrium fluorescence analysis unambiguously ind...
Source: Biochimica et Biophysica Acta - August 11, 2009 Category: Biochemistry Authors: Cattoni DI, Kaufman SB, González Flecha FL Tags: Biochim Biophys Acta Source Type: journals

Chromosomal tethering and proviral integration.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Since integration into the host cell genome is an obligatory step for their replication, retro-elements are both potent insertional mutagens and also suitable vectors for gene therapy. Many recent studies reported that the integration process is not random but, on the contrary, higly regulated at the molecular level. Many viral proteins and cellular factors play a key role in the integration step, explaining the reason why different retro-elements display distinct integration profiles. This review describes the recent highlights about integration of retro-elemnets with particular focus on the mechanisms underlying the ...
Source: Biochimica et Biophysica Acta - August 11, 2009 Category: Biochemistry Authors: Delelis O, Zamborlini A, Thierry S, Saïb A Tags: Biochim Biophys Acta Source Type: journals

Structure, dynamics and mapping of membrane-binding residues of micelle-bound antimicrobial peptides by natural abundance (13)C NMR spectroscopy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Worldwide bacterial resistance to traditional antibiotics has drawn much research attention to naturally occurring antimicrobial peptides (AMPs) owing to their potential as alternative antimicrobials. Structural studies of AMPs are essential for an in-depth understanding of their activity, mechanism of action, and in guiding peptide design. Two-dimensional solution proton NMR spectroscopy has been the major tool. In this article, we describe the applications of natural abundance (13)C NMR spectroscopy that provides complementary information to 2D (1)H NMR. The correlation of (13)Calpha secondary shifts with both 3D str...
Source: Biochimica et Biophysica Acta - August 10, 2009 Category: Biochemistry Authors: Wang G Tags: Biochim Biophys Acta Source Type: journals

Hsp90 transcriptionally and post-translationally regulates the expression of NDRG1 and maintains the stability of its modifying kinase GSK3beta.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
N-myc downstream regulated gene-1 (NRDG1) is a stress-induced protein whose putative function is suppression of tumor metastasis. A recent proteonomic study showed NDRG1 interacts with the molecular chaperone heat shock protein 90 (Hsp90). From their reported association, we investigated if NDRG1 is dependent on Hsp90 for its stability and is therefore a yet unidentified Hsp90 client protein. Here, we demonstrate that endogenous NDRG1 and Hsp90 physically associate in hepatocellular cancer cell lines. However, geldanamycin (GA)-mediated inhibition of Hsp90 did not disrupt their interaction or result in NDRG1 protein de...
Source: Biochimica et Biophysica Acta - August 10, 2009 Category: Biochemistry Authors: Banz VM, Medová M, Keogh A, Furer C, Zimmer Y, Candinas D, Stroka D Tags: Biochim Biophys Acta Source Type: journals

Transcriptional and post-transcriptional regulation of mitochondrial biogenesis in skeletal muscle: Effects of exercise and aging.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Acute contractile activity of skeletal muscle initiates the activation of signaling kinases. This promotes the phosphorylation of transcription factors, leading to enhanced DNA binding and transcriptional activation and/or repression. The mRNA products of nuclear genes encoding mitochondrial proteins are translated in the cytosol and imported into pre-existing mitochondria. When contractile activity is repeated, the recapitulation of these cellular events progressively leads to an expansion of the mitochondrial reticulum within muscle. This has physiologically relevant health benefit, including enhanced lipid metabolis...
Source: Biochimica et Biophysica Acta - August 10, 2009 Category: Biochemistry Authors: Ljubicic V, Joseph AM, Saleem A, Uguccioni G, Collu-Marchese M, Lai RY, Nguyen LM, Hood DA Tags: Biochim Biophys Acta Source Type: journals

Molecular pathology of RUNX3 in human carcinogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A major goal of molecular biology is to elucidate the mechanisms underlying cancer development and progression in order to achieve early detection, better diagnosis and staging and novel preventive and therapeutic strategies. We feel that an understanding of Runt-related transcription factor 3 (RUNX3)-regulated biological pathways will directly impact our knowledge of these areas of human carcinogenesis. The RUNX3 transcription factor is a downstream effector of the transforming growth factor-beta (TGF-beta) signaling pathway, and has a critical role in the regulation of cell proliferation and cell death by apoptosis, ...
Source: Biochimica et Biophysica Acta - August 10, 2009 Category: Biochemistry Authors: Subramaniam MM, Chan JY, Yeoh KG, Quek T, Ito K, Salto-Tellez M Tags: Biochim Biophys Acta Source Type: journals

Tumor cells energy metabolism and its common features with yeast metabolism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
During the last decades a considerable amount of research has been focused on cancer. A number of genetic and signalling defects have been identified. This has allowed the design and screening of a number of anti-tumor drugs for therapeutic use. One of the main challenge of anti-cancer therapy is to specifically target these drugs to malignant cells. Recently, tumor cell metabolism has been considered as a possible target for cancer therapy. It is widely accepted that tumors display an enhanced glycolytic activity and oxidative phosphorylation down-regulation (Warburg effect). Therefore, it seems reasonable that disrup...
Source: Biochimica et Biophysica Acta - August 10, 2009 Category: Biochemistry Authors: Diaz-Ruiz R, Uribe-Carvajal S, Devin A, Rigoulet M Tags: Biochim Biophys Acta Source Type: journals

Mitochondria in Huntington's disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Huntington's disease (HD) is an inherited progressive neurodegenerative disorder associated with involuntary abnormal movements (chorea), cognitive deficits and psychiatric disturbances. The disease is caused by an abnormal expansion of a CAG repeat located in exon 1 of the gene encoding the huntingtin protein (Htt) that confers a toxic function to the protein. The most striking neuropathological change in HD is the preferential loss of medium spiny GABAergic neurons in the striatum. The mechanisms underlying striatal vulnerability in HD are unknown, but compelling evidence suggests that mitochondrial defects may play ...
Source: Biochimica et Biophysica Acta - August 10, 2009 Category: Biochemistry Authors: Damiano M, Galvan L, Déglon N, Brouillet E Tags: Biochim Biophys Acta Source Type: journals

Regulation of neuron mitochondrial biogenesis and relevance to brain health.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mitochondrial dysfunction has severe cellular consequences, and is linked to aging and neurological disorders in humans. Impaired energy supply or Ca(2+) buffering, increased ROS production, or control of apoptosis by mitochondria may contribute to the progressive decline of long-lived postmitotic cells. Mitochondrial biogenesis refers to the process via which cells increase their individual mitochondrial mass. Mitochondrial biogenesis may represent an attempt by cells to increase their aerobic set point, or an attempt to maintain a pre-existing aerobic set point in the face of declining mitochondrial function. Neurona...
Source: Biochimica et Biophysica Acta - August 10, 2009 Category: Biochemistry Authors: Onyango IG, Lu J, Rodova M, Lezi E, Crafter AB, Swerdlow RH Tags: Biochim Biophys Acta Source Type: journals

Cytochrome c oxidase deficiency: Patients and animal models.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cytochrome c oxidase (COX) deficiencies are one of the most common defects of the respiratory chain found in mitochondrial diseases. COX is a multimeric inner mitochondrial membrane enzyme formed by subunits encoded by both the nuclear and the mitochondrial genome. COX biosynthesis requires numerous assembly factors that do not form part of the final complex but participate in prosthetic group synthesis and metal delivery in addition to membrane insertion and maturation of COX subunits. Human diseases associated with COX deficiency including encephalomyopathies, Leigh syndrome, hypertrophic cardiomyopathies, and fatal ...
Source: Biochimica et Biophysica Acta - August 10, 2009 Category: Biochemistry Authors: Diaz F Tags: Biochim Biophys Acta Source Type: journals

"Short-chain" alpha-1,4-glucan phosphorylase having a truncated N-terminal domain: Functional expression and characterization of the enzyme from Sulfolobus solfataricus.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
All known alpha-1,4-glucan phosphorylases (GPs) are active as homodimers and use their N-terminal domains for oligomerisation. Structure-based sequence comparison of a putative phosphorylase from the thermophilic crenarchaeon Sulfolobus solfataricus (SsGP) with the well characterized GP from Escherichia coli reveals that SsGP totally lacks the otherwise conserved regions for building the dimer interface. Because all efforts of producing functional SsGP in E. coli failed, we used heterologous gene expression in the hyperthermophilic archaeon Thermococcus kodakaraensis and isolated, in low amounts, SsGP harboring Strep-T...
Source: Biochimica et Biophysica Acta - August 10, 2009 Category: Biochemistry Authors: Müller M, Takemasa R, Schwarz A, Atomi H, Nidetzky B Tags: Biochim Biophys Acta Source Type: journals