Modulation of the p53/MDM2 interplay by HAUSP inhibitors

作     者：Omid Tavana Wei GU 

作者机构：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 

出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)

年 卷 期：2017年第9卷第1期

页      面：45-52页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 09[农学] 

基　　金：TheNationalCancerInstitute,USNationalInstitutesofHealth(NIH)(5R01CA193890,5R01CA190477,5R01CA085533,2P01CA080058toW.G.) TheNIHCancerBiologyTrainingGrantT32-CA09503) 

主　　题：HAUSP USP7 p53 stability MDM2 stability HAUSP inhibitors cancer 

摘      要：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 deu- biquitinase 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.