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. 2012 Sep 4;287(43):36443–36454. doi: 10.1074/jbc.M112.374157

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© 2012 by The American Society for Biochemistry and Molecular Biology, Inc.

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FIGURE 9. — Proposed model for the effect of p53-HEXIM1 interaction on the induction of p53. Our results suggest that two regulatory mechanisms are utilized by HEXIM1 to enhance the protein stability of p53: 1) HEXIM1 directly binds to p53 and protects p53 from being ubiquitinated by HDM2. The p53-HEXIM1 interaction can be induced by UV, CDK inhibitors, transcription inhibitors, and p53 inducers. 2) HEXIM1 binds to HDM2 and is subsequently ubiquitinated by HDM2. Therefore, this HEXIM1-HDM2 interaction indirectly protects a portion of p53 from being ubiquitinated by HDM2. Flavo, flavopiridol; Ros, roscovitine; ActD, actinomycin D; Dox, doxorubicin; Etop, etoposide; Nut, nutlin-3.