Chemotherapy induces NEDP1-mediated destabilization of MDM2

  title={Chemotherapy induces NEDP1-mediated destabilization of MDM2},
  author={Ian R. Watson and Bing Keong Li and Olga Roche and Alvaro Blanch and Michael Ohh and Meredith S Irwin},
MDM2 is an E3 ligase that promotes ubiquitin-mediated destruction of p53. Cellular stresses such as DNA damage can lead to p53 activation due in part to MDM2 destabilization. Here, we show that the stability of MDM2 is regulated by an ubiquitin-like NEDD8 pathway and identify NEDP1 as a chemotherapy-induced isopeptidase that deneddylates MDM2, resulting in MDM2 destabilization concomitant with p53 activation. Concordantly, RNAi-mediated knockdown of endogenous NEDP1 blocked diminution of MDM2… CONTINUE READING

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