title: Modulation of the p53/MDM2 interplay by HAUSP inhibitors.
abstract: 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.
authors.affiliation: College of Physicians and Surgeons, Institute for Cancer Genetics, Columbia University, New York, NY 10032, USA.|Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Omid
authors.initials: O
authors.lastname: Tavana
authors.affiliation: College of Physicians and Surgeons, Institute for Cancer Genetics, Columbia University, New York, NY 10032, USA.|Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.|Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Gu
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000037:antagonists & inhibitors / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2; D043222:Ubiquitin Thiolesterase
keywords: HAUSP; HAUSP inhibitors; MDM2 stability; USP7; cancer; p53 stability