p53 Binding to the p21 promoter is dependent on the nature of DNA damage
Abstract
p53 Is a tumor suppressor that integrates signals from different stress induced signalling pathways, regulates cell cycle arrest, senescence, apoptosis and DNA repair. How p53 dictates cell fate is unclear. As a major transcriptional target of p53 in response to cellular stress, p21 is a key component in cell cycle control and apoptosis, directing an anti-apoptotic response following DNA damage. It is therefore likely that p53-dependent regulation of p21 contributes, at least in part, how p53 influences cellular outcome upon DNA damage. Here we compare the p53-dependent transcriptional regulation of p21 in response to DNA damage by ultraviolet (UV) radiation and ionizing radiation (IR). We demonstrate that despite comparable levels of p53 accumulation by both types of DNA damage, IR causes significant, early accumulation of p21 not seen in UV-damaged cells, with a substantially different cell cycle profile. Whereas UV and IR both target p21 protein for degradation immediately after DNA damage, differential post-damage p21 transcription is accountable for the disparity in p21 protein levels. Chromatin immunoprecipitation studies reveal that p53 displays a clear bias against the p21 promoter in UV-damaged cells compared to IR-dam...Continue Reading
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Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis