title: USP11 regulates p53 stability by deubiquitinating p53.
abstract: The p53 tumor suppressor protein coordinates the cellular responses to a broad range of cellular stresses, leading to DNA repair, cell cycle arrest or apoptosis. The stability of p53 is essential for its tumor suppressor function, which is tightly controlled by ubiquitin-dependent degradation primarily through its negative regulator murine double minute 2 (Mdm2). To better understand the regulation of p53, we tested the interaction between p53 and USP11 using co-immunoprecipitation. The results show that USP11, an ubiquitin-specific protease, forms specific complexes with p53 and stabilizes p53 by deubiquitinating it. Moreover, down-regulation of USP11 dramatically attenuated p53 induction in response to DNA damage stress. These findings reveal that USP11 is a novel regulator of p53, which is required for p53 activation in response to DNA damage.
authors.affiliation: College of Chemistry and Life Science, Quanzhou Normal University, Quanzhou 36200, China; The Higher Educational Key Laboratory for Molecular Biology and Pharmacology of Fujian Province, Quanzhou 36200, China; Xiamen Women and Children Health Hospital, Xiamen 361005, China; Shouguang People's Hospital, Shouguang 262700, China; Department of Orthopedics, Central Hospital of Zibo, Zibo 255000, China; Department of Pathology, University of Chicago, Chicago 60102, Illinois, USA; Department of Pathology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 36200, China.
authors.forename: Jia-ying
authors.initials: JY
authors.lastname: Ke
authors.forename: Cong-jie
authors.initials: CJ
authors.lastname: Dai
authors.forename: Wen-lin
authors.initials: WL
authors.lastname: Wu
authors.forename: Jin-hua
authors.initials: JH
authors.lastname: Gao
authors.forename: Ai-juan
authors.initials: AJ
authors.lastname: Xia
authors.forename: Guang-ping
authors.initials: GP
authors.lastname: Liu
authors.forename: Kao-sheng
authors.initials: KS
authors.lastname: Lv
authors.forename: Chun-lin
authors.initials: CL
authors.lastname: Wu
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle; D045744:Cell Line, Tumor; D003513:Cycloheximide / Q000737:chemistry; D004249:DNA Damage; D004260:DNA Repair; D057809:HEK293 Cells; D006801:Humans; D010957:Plasmids / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D034622:RNA Interference; D013869:Thiolester Hydrolases / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C101359:USP11 protein, human; D025801:Ubiquitin; D003513:Cycloheximide; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D013869:Thiolester Hydrolases
keywords: Deubiquitination; Stability; USP11; p53