Function And Structure Of The Protein P5 On A Molecular Level

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Function and structure of the protein P5 on a molecular level

Function and structure of the protein P5 on a molecular level


P53, also known as TP53 or tumor protein (EC: is a gene that codes for a protein that regulates the cell cycle and hence functions as a tumor suppression. It is very important for cells in multicellular organisms to suppress cancer. P53 has been described as "the guardian of the genome", referring to its role in conserving stability by preventing genome mutation (Harms KL, Chen X 2005). The name is due to its molecular mass: it is in the 53 kilodalton fraction of cell proteins. The p53 tumor suppressor gene is one of the most frequently mutated genes in human cancers (Bell S, Klein C, Muller L, Hansen S, Buchner J. 2002). It is a cell cycle checkpoint gene responsible for committing mammalian cells to a growth arrest phenotype or apoptosis in response to genotoxic and non-genotoxic stressors. The p53 gene encodes a transcription factor that is synthesized in a latent form and can be activated by a wide range cell stressors. Once activated, the intracellular p53 protein level increases and p53 binds, in sequence-specific fashion, to certain DNA promoters which, in turn, leads to activation of genes that mediate cell cycle arrest.

One of the p53 responsive genes that appears necessary for mediating G1 arrest in several cell types is p21WAF1/CIP1, a cyclin-dependent kinase inhibitor (Bell S, Klein C, Muller L, Hansen S, Buchner J. 2002). Activation of p53 is complex and inhibition of this process can lead to loss of cell growth control. Activation of p53 is thought to take place at both the translational and post-translational level. Most recent work has concentrated on understanding the post-translational events that lead to p53 activation. The exact activation pathway is highly dependent on the type of stressor applied. Each class of stressors appears to result in a unique pattern of p53 protein phosphorylation and acetylation to achieve p53-mediated transcription of appropriate downstream targets (Giaccia and Kastan, 1998). Concomitant with these modifications p53 protein levels increase. Another potential post-translational modification system less extensively explored is direct p53 redox regulation. Protein redox alterations in response to environmental agents, was proposed to occur more than four decades ago but it is only within the past 5 years that, with the advent of new techniques, solid evidence has accumulated indicating that redox changes can occur on cytoplasmic proteins in vivo Table 1 lists a partial set of cytoplasmic proteins that have been shown to be oxidized at cysteine residues in cells and the effect of oxidation on their activities. For illustrative purposes, a few of these will be discussed.




p53 was identified in 1979 by Arnold Levine,David Lane and William Old,working at Princeton University, Dundee University (UK) and Sloan-Kettering Memorial Hospital, respectively. It had been hypothesized to exist before as the target of the SV40 virus, a strain that induced development of tumors.Although it was initially presumed to be an oncogene, its character ...
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