Decision Making by p53: Life versus Death.

Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, New York.
Molecular and Cellular Pharmacology 01/2010; 2(2):69-77. DOI: 10.4255/mcpharmacol.10.10
Source: PubMed

ABSTRACT Cellular response to DNA damage is multifacted in nature and involves a complex signaling network in which p53 functions as a "molecular node" for converging signals. p53 has been implicated in a variety of cellular processes primarily functioning as a transcription factor and also in a transcription-independent manner. It is rapidly activated following DNA damage with phosphorylation as one of the initial signals. Cellular context as well as the type and severity of DNA damage determine p53 activation code, and its activities are regulated predominantly through protein degradation, post-translational modification and interactions with various cellular co-factors. These events are crucial in decision making by p53 as it has the ability to receive, assess and integrate different signals and route them accordingly to induce cell death or promote cell survival. In this decision making process, its transcriptional role to activate a specific subset of target genes linked to inducing cell cycle arrest or apoptosis is critical that is further fine-tuned by its transcription-independent function. This article reviews the current state of knowledge about the role of p53 in determining the fate of cells that have incurred DNA damage.

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Available from: Lingyan Jiang, Dec 19, 2013
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    • "Turnover of p53 is controlled primarily by E3 ubiquitin ligases, such as HDM2, that target p53 for degradation by 26S proteasomes. Disruption of the p53–HDM2 interaction, for example, by competition or posttranslational modifications of p53 and/or HDM2, leads to a rapid accumulation of p53 after stress [Jiang et al., 2010]. The results presented here indicate that SEPW1 promotes cell cycle progression because it increases ubiquitination and proteasomal degradation of p53. "
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    • "hat lower concentration , such as 50lM , triggered the G2 / M phase arrest , whereas concentrations exceeding 150lM causes apoptosis ( Chang et al . , 2011 ) . The p53 protein plays a key role in the DNA damage response pathway by transmitting a variety of stress signals associated with antiproliferative cellular responses that lead to apoptosis ( Jiang et al . , 2010 ) . In response to CTN - induced DNA damage , overexpression of p53 protein leading to upregulation of p21 / waf1 was also observed , which results in arrest of the cell cycle progression at the G0 / G1 or G2 / M phases ( Abbas and Dutta , 2009 ) . CTN exposure also leads to upregulation of the proapoptotic protein Bax and suppression o"
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