Regulation of p53 after Different Forms of Stress and at Different Cell Cycle Stages

Numerous forms of cellular stress activate pathwaysthat result in accumulation of the p53 tumor suppressorprotein (Giaccia and Kastan 1998; Prives 1998). p53 protein levels are generally regulated posttranscriptionally,and it is well documented that increases in p53 resultfrom reduction of its normally high rate of proteasomemediated turnover (Maki et al. 1996). In most (but not all)cases, increasing the cellular quantities of p53 results inthe initiation of a transcriptional program in which a subset of genes that regulate cell cycle and/or death are induced in some cases and repressed in others (Yu et al.1999; Zhao et al. 2000). Induction of most p53 targets results from its function as a sequence-specific transcriptional activator (Vogelstein and Kinzler 1992). Less isunderstood as to how p53 causes some of its targets to berepressed, although its ability to interact with the histonedeacetylase mSin3A may be involved in some cases(Murphy et al. 1999)...