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


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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    • "This was achieved by selection of a cell line with reduced metabolic activity and reduction of the incubation time to 4 h (Pieterse et al. 2013). The p53 CALUX is a reporter assay that quantifies activity mediated by the p53 protein which is the major regulator for cellular responses towards genotoxicity such as cell cycle arrest, activation of DNA repair mechanisms, and initiation of apoptosis (van der Linden et al. 2014; Jiang et al. 2010). Since various compounds may only elicit genotoxic effects after metabolic activation (for which the U2OS cell line has very limited capability; Geiger et al. 2012; Beck et al. 2013), the p53 CALUX may be complemented with an in vitro metabolizing system such as microsomal S9 fractions. "
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