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Cellular Signaling Pathways (cellular + signaling_pathway)
Selected AbstractsCharting protein complexes, signaling pathways, and networks in the immune systemIMMUNOLOGICAL REVIEWS, Issue 1 2006Angela Bauch Summary:, Systematic deciphering of protein,protein interactions has the potential to generate comprehensive and instructive signaling networks and to fuel new therapeutic and diagnostic strategies. Here, we describe how recent advances in high-throughput proteomic technologies, involving biochemical purification methods and mass spectrometry analysis, can be applied systematically to the characterization of protein complexes and the computation of molecular networks. The networks obtained form the basis for further functional analyses, such as knockdown by RNA interference, ultimately leading to the identification of nodes that represent candidate targets for pharmacological exploitation. No individual experimental approach can accurately elucidate all critical modulatory components and biological aspects of a signaling network. Such functionally annotated protein,protein interaction networks, however, represent an ideal platform for the integration of additional datasets. By providing links between molecules, they also provide links to all previous observations associated with these molecules, be they of genetic, pharmacological, or other origin. As exemplified here by the analysis of the tumor necrosis factor (TNF)-,/nuclear factor-,B (NF-,B) signaling pathway, the approach is applicable to any mammalian cellular signaling pathway in the immune system. [source] REVIEW ARTICLE: How to make a melanoma: what do we know of the primary clonal events?PIGMENT CELL & MELANOMA RESEARCH, Issue 1 2008Dorothy C. Bennett Summary Rapid advances have been made in our knowledge of the commonest genetic and epigenetic alterations found in human sporadic melanomas. Valuable recent contributions came from analyses of gene copy number by comparative genome hybridization, and from large-scale gene expression profiling. All of the commonest affected genes encode regulatory components. Loci with established importance in melanoma, like CDKN2A, BRAF and PTEN, have been joined by some less familiar genes including transcription factor sequences TBX2 and STK11 (LKB). This knowledge is reviewed in relation to the cellular signaling pathways affected by these molecules, their biological outcomes, and the implications as to what changes are required overall to generate a melanoma. The data support a model in which genesis of melanoma requires changes that (1) initiate clonal expansion, (2) overcome cell senescence, and (3) reduce apoptosis. [source] Body fluid proteomics: Prospects for biomarker discoveryPROTEOMICS - CLINICAL APPLICATIONS, Issue 9 2007Sung-Min Ahn Abstract Many diseases are caused by perturbations of cellular signaling pathways and related pathway networks as a result of genetic aberrations. These perturbations are manifested by altered cellular protein profiles in the fluids bathing tissue/organs (i.e., the tissue interstitial fluid, TIF). A major challenge of clinical chemistry is to quantitatively map these perturbed protein profiles , the so-called "signatures of disease" , using modern proteomic technologies. This information can be utilized to design protein biomarkers for the early detection of disease, monitoring disease progression and efficacy of drug action. Here, we discuss the use of body fluids in the context of prospective biomarker discovery, and the marked 1000,1500-fold dilution of body fluid proteins, during their passage from TIF to the circulatory system. Further, we discuss proteomics strategies aimed at depleting major serum proteins, especially albumin, in order to focus on low-abundance protein/peptides in plasma. A major limitation of depletion strategies is the removal of low-molecular weight protein/peptides which specifically bind major plasma proteins. We present a prototype model, using albumin, for understanding the multifaceted nature of biomarker research, highlighting the involvement of albumin in Alzheimer's disease. This model underscores the need for a system-level understanding for biomarker research and personalized medicine. [source] Iron in neuronal function and dysfunctionBIOFACTORS, Issue 2 2010Gabriela A. Salvador Abstract Iron (Fe) is an essential element for many metabolic processes, serving as a cofactor for heme and nonheme proteins. Cellular iron deficiency arrests cell growth and leads to cell death; however, like most transition metals, an excess of intracellular iron is toxic. The ability of Fe to accept and donate electrons can lead to the formation of reactive nitrogen and oxygen species, and oxidative damage to tissue components; contributing to disease and, perhaps, aging itself. It has also been suggested that iron-induced oxidative stress can play a key role in the pathogenesis of several neurodegenerative diseases. Iron progressively accumulates in the brain both during normal aging and neurodegenerative processes. However, iron accumulation occurs without the concomitant increase in tissue ferritin, which could increase the risk of oxidative stress. Moreover, high iron concentrations in the brain have been consistently observed in Alzheimer's disease (AD) and Parkinson's disease (PD). In this regard, metalloneurobiology has become extremely important in understanding the role of iron in the onset and progression of neurodegenerative diseases. Neurons have developed several protective mechanisms against oxidative stress, among them the activation of cellular signaling pathways. The final response will depend on the identity, intensity, and persistence of the oxidative insult. The characterization of the mechanisms involved in high iron induced in neuronal dysfunction and death is central to understanding the pathology of a number of neurodegenerative disorders. [source] | ||||||||||