Regulation of p53 by MDM2. p53 and MDM2 form an autoregulatory feedback loop. p53 stimulates the expression of MDM2; MDM2, in turn, inhibits p53 activity.

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Regulation of p53 by MDM2. p53 and MDM2 form an autoregulatory feedback loop. p53 stimulates the expression of MDM2; MDM2, in turn, inhibits p53 activity because it stimulates its degradation in the nucleus and the cytoplasm, blocks its transcriptional acti... Regulation of p53 by MDM2. p53 and MDM2 form an autoregulatory feedback loop. p53 stimulates the expression of MDM2; MDM2, in turn, inhibits p53 activity because it stimulates its degradation in the nucleus and the cytoplasm, blocks its transcriptional activity, and promotes its nuclear export. A broad range of DNA damaging agents or deregulated oncogenes induces p53 activation. DNA damage promotes phosphorylation of p53 and MDM2, thereby preventing their interaction and stabilizing p53. Likewise, activated oncogenes induce ARF protein, which sequesters MDM2 into the nucleolus, thus preventing the degradation of p53. Conversely, survival signals mediate nuclear import of MDM2 via Akt activation, which destabilizes p53. Ute M. Moll, and Oleksi Petrenko Mol Cancer Res 2003;1:1001-1008 ©2003 by American Association for Cancer Research