Mdm2 targets the p53 transcription cofactor JMY for degradation

  • Coutts A
  • Boulahbel H
  • Graham A
 et al. 
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Abstract

We define here a new mechanism through which Mdm2 (mouse double minute 2) regulates p53 activity, by targeting the p53 transcription cofactor JMY. DNA damage causes an increase in JMY protein, and, in a similar manner, small molecule inhibitors of Mdm2 activity induce JMY in unperturbed cells. At a mechanistic level, Mdm2 regulation of JMY requires the Mdm2 RING (really interesting new gene) finger, which promotes the ubiquitin-dependent degradation of JMY. However, regulation of JMY occurs independently of the p53-binding domain in Mdm2 and p53 activity. These results define a new functional relationship between the p53 cofactor JMY and Mdm2, and indicate that transcription cofactors that facilitate p53 activity are important targets for Mdm2 in suppressing the p53 response.

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Authors

  • Amanda S. Coutts

  • Houda Boulahbel

  • Anne Graham

  • Nicholas B. La Thangue

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