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Modulation of the p53/MDM2 interplay by HAUSP inhibitors Free
Omid Tavana1,2,*, and Wei Gu1,2,3,*
1 College of Physicians and Surgeons, Institute for Cancer Genetics, Columbia University, New York, NY 10032, USA
2 Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
3 Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA *Correspondence to:Omid Tavana, E-mail: ot2169@cumc.columbia.edu; Wei Gu, E-mail:wg8@cumc.columbia.edu
J Mol Cell Biol, Volume 9, Issue 1, February 2017, Pages 45-52  https://doi.org/10.1093/jmcb/mjw049
Keyword: HAUSP, USP7, p53 stability, MDM2 stability, HAUSP inhibitors, cancer

It is well established that both p53 and MDM2 are short-lived proteins whose stabilities are tightly controlled through ubiquitination-mediated degradation. Although numerous studies indicate that the MDM2 E3 ligase activity, as well as the protein–protein interaction between p53 and MDM2, is the major focus for this regulation, emerging evidence suggests that the deubiquitinase herpesvirus-associated ubiquitin-specific protease (HAUSP, also known as USP7) plays a critical role. Furthermore, HAUSP inhibition elevates p53 stability and might be beneficial for therapeutic purposes. In this review, we discuss the advances of this dynamic pathway and the contributions of positive and negative regulators affecting HAUSP activity. We also highlight the roles of HAUSP in cancer justifying the production of the first generation of HAUSP inhibitors.