When normal mammalian cells are subjected to stress signals -oxygen deficiency, radiation, DNA damage or chemotherapeutic drugs, for example - the 'guardian of the genome', p53, is woken up. Then, p53-dependent gene transcription is increased and ubiqui-tin-dependent degradation of the protein is blocked, all of which leads to the p53-mediated induction of programmed cell death and/or cell-cycle arrest. But how do such stress signals awaken p53? One idea is that stress-activated protein kinases modify p53, protecting it from degradation and activating its function as a transcription factor. In support of this theory, many phos-phorylated forms of p53 are found in cells. Moreover, p53 can exist in a latent state that cannot bind DNA, and it can be released from this state by phosphorylation.
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