Home About us Contact
|
Home About us Contact | ||
|
|
||
Diverse Cellular Processes (diverse + cellular_process)
Selected AbstractsDeath-associated protein kinase (DAPK) and signal transduction: additional roles beyond cell deathFEBS JOURNAL, Issue 1 2010Yao Lin Death-associated protein kinase (DAPK) is a stress-regulated protein kinase that mediates a range of processes, including signal-induced cell death and autophagy. Although the kinase domain of DAPK has a range of substrates that mediate its signalling, the additional protein interaction domains of DAPK are relatively ill defined. This review will summarize our current knowledge of the DAPK interactome, the use of peptide aptamers to define novel protein,protein interaction motifs, and how these new protein,protein interactions give insight into DAPK functions in diverse cellular processes, including growth factor signalling, the regulation of autophagy, and its emerging role in the regulation of immune responses. [source] Green fluorescent protein , a bright idea for the study of bacterial protein localizationFEMS MICROBIOLOGY LETTERS, Issue 1 2001Gregory J Phillips Abstract Use of the green fluorescent protein (GFP) of Aequorea victoria as a reporter for protein and DNA localization has provided sensitive, new approaches for studying the organization of the bacterial cell, leading to new insights into diverse cellular processes. GFP has many characteristics that make it useful for localization studies in bacteria, primarily its ability to fluoresce when fused to target polypeptides without the addition of exogenously added substrates. As an alternative to immunofluorescence microscopy, the expression of gfp gene fusions has been used to probe the function of cellular components fundamental for DNA replication, translation, protein export, and signal transduction, that heretofore have been difficult to study in living cells. Moreover, protein and DNA localization can now be monitored in real time, revealing that several proteins important for cell division, development and sporulation are dynamically localized throughout the cell cycle. The use of additional GFP variants that permit the labeling of multiple components within the same cell, and the use of GFP for genetic screens, should continue to make this a valuable tool for addressing complex questions about the bacterial cell. [source] Down-regulation of the PI3-kinase/Akt pathway by ERK MAP kinase in growth factor signalingGENES TO CELLS, Issue 9 2008Hideko Hayashi The ERK MAP kinase and PI3-kinase/Akt pathways are major intracellular signaling modules, which are known to regulate diverse cellular processes including cell proliferation, survival and malignant transformation. However, it has not been fully understood how these two pathways interact with each other. Here, we demonstrate that inhibition of the ERK pathway by the MEK inhibitor U0126 or PD98059 significantly potentiates EGF- and FGF-induced Akt phosphorylation at both Thr308 and Ser473. We also show that hyperactivation of the ERK pathway greatly attenuates EGF- and FGF-induced Akt phosphorylation. Furthermore, the enhanced Akt phosphorylation induced by U0126 is inhibited by the PI3-kinase inhibitor LY294002, and is accompanied by the up-regulation of Ras activity. These results suggest that the ERK pathway inhibition enhances Akt phosphorylation through the Ras/PI3-kinase pathway. Thus, our results demonstrate that the ERK pathway negatively modulates the PI3-kinase/Akt pathway in response to growth factor stimulation. [source] AAA+ superfamily ATPases: common structure,diverse functionGENES TO CELLS, Issue 7 2001Teru Ogura The AAA+ superfamily of ATPases, which contain a homologous ATPase module, are found in all kingdoms of living organisms where they participate in diverse cellular processes including membrane fusion, proteolysis and DNA replication. Recent structural studies have revealed that they usually form ring-shaped oligomers, which are crucial for their ATPase activities and mechanisms of action. These ring-shaped oligomeric complexes are versatile in their mode of action, which collectively seem to involve some form of disruption of molecular or macromolecular structure; unfolding of proteins, disassembly of protein complexes, unwinding of DNA, or alteration of the state of DNA,protein complexes. Thus, the AAA+ proteins represent a novel type of molecular chaperone. Comparative analyses have also revealed significant similarities and differences in structure and molecular mechanism between AAA+ ATPases and other ring-shaped ATPases. [source] Involvement of the cytoskeletal elements in articular cartilage homeostasis and pathologyINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 1 2009Emma J. Blain Summary The cytoskeleton of all cells is a three-dimensional network comprising actin microfilaments, tubulin microtubules and intermediate filaments. Studies in many cell types have indicated roles for these cytoskeletal proteins in many diverse cellular processes including alteration of cell shape, movement of organelles, migration, endocytosis, secretion, cell division and extracellular matrix assembly. The cytoskeletal networks are highly organized in structure enabling them to fulfil their biological functions. This review will primarily focus on the organization and function of the three major cytoskeletal networks in articular cartilage chondrocytes. Articular cartilage is a major load-bearing tissue of the synovial joint; it is well known that the cytoskeleton acts as a physical interface between the chondrocytes and the extracellular matrix in ,sensing' mechanical stimuli. The effect of mechanical load on cytoskeletal element expression and organization will also be reviewed. Abnormal mechanical load is widely believed to be a risk factor for the development of osteoarthritis. Several studies have intimated that the major cytoskeletal networks are disorganized or often absent in osteoarthritic cartilage chondrocytes. The implications and possible reasoning for this are more widely discussed and placed into context with their potential relevance to disease and therapeutic strategies. [source] Epigenetic boundaries of tumour suppressor gene promoters: the CTCF connection and its role in carcinogenesisJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 3 2006Felix Recillas-Targa Abstract Genetic and epigenetic regulations are essential mechanisms that ensure proper early and subsequent mammalian programming of diverse cellular processes. These mechanisms affect transcriptional regulation, stem cell determination and cell cycle control, including senescence and aging. It is not surprising that perturbation of the exquisite balance between genetic and epigenetic regulation can lead to diverse diseases, including cancer. Histone covalent modifications and DNA methylation do not explain all epigenetic phenomena. We describe a previously unsuspected epigenetic factor and propose the incorporation of the 11-zinc finger CCCTC-binding factor, known as CTCF as a novel and multifunctional epigenetic regulator. [source] Differential control of apoptosis by DJ-1 in prostate benign and cancer cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2004Yaacov Hod Abstract DJ-1 is a conserved protein reported to be involved in diverse cellular processes ranging from cellular transformation, control of protein,RNA interaction, oxidative stress response to control of male infertility, among several others. Mutations in the human gene have been shown to be associated with an autosomal recessive, early onset Parkinson's disease (PARK7). The present study examines the control of DJ-1 expression in prostatic benign hyperplasia (BPH-1) and cancer (PC-3) cell lines in which DJ-1 abundance differs significantly. We show that while BPH-1 cells exhibit low basal level of DJ-1 expression, stress-inducing agents such as H2O2 and mitomycin C markedly increase the intracellular level of the polypeptide. In contrast, DJ-1 expression is relatively high in PC-3 cells, and incubation with the same cytotoxic drugs does not modulate further the level of the polypeptide. In correlation with the expression of DJ-1, both cytotoxic agents activate the apoptotic pathway in the prostatic benign cells but not in PC-3 cells, which are resistant to their action. We further demonstrate that incubation of BPH-1 cells with TNF-related-apoptosis-inducing-ligand/Apo-2L (TRAIL) also enhances DJ-1 expression and that TRAIL and H2O2 act additively to stimulate DJ-1 accumulation but synergistically in the activation of the apoptotic pathway. Time-course analysis of DJ-1 stimulation shows that while DJ-1 level increases without significant lag in TRAIL-treated cells, there is a delay in H2O2 -treated cells, and that the increase in DJ-1 abundance precedes the activation of apoptosis. Unexpectedly, over-expression of DJ-1 de-sensitizes BPH-1 cells to the action of apoptotic-inducing agents. However, RNA-interference-mediated silencing of DJ-1 expression results in sensitization of PC-3 cells to TRAIL action. These results are consistent with a model in which DJ-1 is involved in the control of cell death in prostate cell lines. DJ-1 appears to play a differential role between cells expressing a low but inducible level of DJ-1 (e.g., BPH-1 cells) and those expressing a high but constitutive level of the polypeptide (e.g., PC-3 cells). © 2004 Wiley-Liss, Inc. [source] Mechanochemical ATPases and transcriptional activationMOLECULAR MICROBIOLOGY, Issue 4 2002X. Zhang Summary Transcriptional activator proteins that act upon the ,54 -containing form of the bacterial RNA polymerase belong to the extensive AAA+ superfamily of ATPases, members of which are found in all three kingdoms of life and function in diverse cellular processes, often via chaperone-like activities. Formation and collapse of the transition state of ATP for hydrolysis appears to engender the interaction of the activator proteins with ,54 and leads to the protein structural transitions needed for RNA polymerase to isomerize and engage with the DNA template strand. The common oligomeric structures of AAA+ proteins and the crea-tion of the active site for ATP hydrolysis between protomers suggest that the critical changes in protomer structure required for productive interactions with ,54 -holoenzyme occur as a consequence of sensing the state of the , -phosphate of ATP. Depending upon the form of nucleotide bound, different functional states of the activator are created that have distinct substrate and chaperone-like binding activ-ities. In particular, interprotomer ATP interactions rely upon the use of an arginine finger, a situation reminiscent of GTPase-activating proteins. [source] The PTEN,AKT3 signaling cascade as a therapeutic target in melanomaPIGMENT CELL & MELANOMA RESEARCH, Issue 4 2009SubbaRao V. Madhunapantula Summary Melanocytes undergo extensive genetic changes during transformation into aggressive melanomas. These changes deregulate genes whose aberrant activity promotes the development of this disease. The phosphoinositide-3-kinase (PI3K) and mitogen-activated protein (MAP) kinase pathways are two key signaling cascades that have been found to play prominent roles in melanoma development. These pathways relay extra-cellular signals via an ordered series of consecutive phosphorylation events from cell surface throughout the cytoplasm and nucleus regulating diverse cellular processes including proliferation, survival, invasion and angiogenesis. It is generally accepted that therapeutic agents would need to target these two pathways to be an effective therapy for the long-term treatment of advanced-stage melanoma patients. This review provides an overview of the PI3 kinase pathway focusing specifically on two members of the pathway, called PTEN and Akt3, which play important roles in melanoma development. Mechanisms leading to deregulation of these two proteins and therapeutic implications of targeting this signaling cascade to treat melanoma are detailed in this review. [source] Structure of a highly stable mutant of human fibroblast growth factor 1ACTA CRYSTALLOGRAPHICA SECTION D, Issue 1 2009Anna Szlachcic Fibroblast growth factors (FGFs) are involved in diverse cellular processes such as cell migration, angiogenesis, osteogenesis, wound healing and embryonic and foetal development. Human acidic fibroblast growth factor (FGF-1) is the only member of the FGF family that binds with high affinity to all four FGF receptors and thus is considered to be the human mitogen with the broadest specificity. However, pharmacological applications of FGF-1 are limited owing to its low stability. It has previously been reported that the introduction of single mutations can significantly improve the stability of FGF-1 and its resistance to proteolytic degradation. Here, the structure of the Q40P/S47I/H93G triple mutant of FGF-1, which exhibits much higher stability, a prolonged half-life and enhanced mitogenic activity, is presented. Compared with the wild-type structure, three localized conformational changes in the stable triple mutant were observed, which is in agreement with the perfect energetic additivity of the single mutations described in a previous study. The huge change in FGF-1 stability (the denaturation temperature increased by 21.5,K, equivalent to ,,Gden = 24.3,kJ,mol,1) seems to result from the formation of a short 310 -helix (position 40), an improvement in the propensity of amino acids to form ,-sheets (position 47) and the rearrangement of a local hydrogen-bond network (positions 47 and 93). [source] Crystallization and preliminary X-ray crystallographic analysis of the N domain of p97/VCP in complex with the UBX domain of FAF1ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 1 2010Hwa Young Shin p97/VCP is a multifunctional AAA+ -family ATPase that is involved in diverse cellular processes. p97/VCP directly interacts with various adaptors for activity in different biochemical contexts. Among these adaptors are p47 and Fas-associated factor 1 (FAF1), which contain a common UBX domain through which they bind to the N domain of p97/VCP. In the ubiquitin,proteasome pathway, p97/VCP acts as a chaperone that presents client proteins to the proteasome for degradation, while FAF1 modulates the process by interacting with ubiquitinated client proteins and also with p97/VCP. In an effort to elucidate the structural details of the interaction between p97/VCP and FAF1, the p97/VCP N domain was crystallized in complex with the FAF1 UBX domain. X-ray data were collected to 2.60,Å resolution and the crystals belonged to space group C2221, with unit-cell parameters a = 58.24, b = 72.81, c = 132.93,Å. The Matthews coefficient and solvent content were estimated to be 2.39,Å3,Da,1 and 48.4%, respectively, assuming that the asymmetric unit contained p97/VCP N domain and FAF1 molecules in a 1:1 ratio, which was subsequently confirmed by molecular-replacement calculations. [source] To SIR with Polycomb: linking silencing mechanismsBIOESSAYS, Issue 2 2005Vivek S. Chopra Yeast SIR2, the most evolutionarily conserved deacetylase, plays an essential role in epigenetic silencing at the silent mating type loci and telomeres. SIR2 has been implicated in chromatin silencing and lifespan determination in several organisms. Discovery that Drosophila SIR2 is also involved in epigenetic silencing mediated by the Polycomb group proteins and is physically associated with a complex containing the E(Z) histone methyltransferase1 has wide implications. These findings suggest possible link of Polycomb system to diverse cellular processes including senescence. BioEssays 27:119,121, 2005. © 2005 Wiley Periodicals, Inc. [source] | ||||||||||||||||