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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.

Original publication

DOI

10.1038/sj.embor.7400855

Type

Journal article

Journal

EMBO Rep

Publication Date

01/2007

Volume

8

Pages

84 - 90

Keywords

Animals, Carrier Proteins, Cells, Cultured, DNA Damage, Humans, Mice, Nuclear Proteins, Trans-Activators, Transcription Factors, Tumor Suppressor Protein p53, Ubiquitin