期刊
EMBO REPORTS
卷 8, 期 1, 页码 84-90出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.embor.7400855
关键词
cancer; p53 response; Mdm2; transcription
资金
- MRC [G0500905, G9400953] Funding Source: UKRI
- Cancer Research UK [13058] Funding Source: Medline
- Medical Research Council [G9400953, G0500905] Funding Source: Medline
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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