HLA-B-associated transcript 3 (Bat3) stabilizes and activates p53 in a HAUSP-dependent manner  

作　　者：Rui Zhang Di Cui TengXue Yue Lang Yunfan Zhang Lianjie Li Haili Sun Yu Kuang Gebin Li Jun Tang 

机构地区：[1]Department of Basic Veterinary,College of Veterinary Medicine,China Agricultural University,Beijing 100193,China [2]State Key Laboratory of Agrobiotechnology,China Agricultural University,Beijing 100193,China [3]Department of Clinical Veterinary,College of Veterinary Medicine,China Agricultural University,Beijing 100193,China [4]Clinical Research Institute,Zhejiang Provincial People's Hospital,People's Hospital of Hangzhou Medical College,Hangzhou 310014,China

出　　处：《Journal of Molecular Cell Biology》2020年第2期99-112,共14页分子细胞生物学报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(31500703,31371351,and 31671488);the Program for New Century Excellent Talents in University of China(NCET-09-0737).

摘　　要：The p53 pathway is a highly complex signaling network including several key regulators.HAUSP is a critical component of the p53 pathway acting as a deubiquitinase for both p53 and its key repressor Mdm2.Here,we identified a novel HAUSP-interacting protein,HLA-B-associated transcript 3(Bat3)and found it to be capable of inducing p53 stabilization and activation via a HAUSP-dependent mechanism,resulting in cell growth inhibition.Surprisingly,the deubiquitylating enzymatic activity of HAUSP was not required for this phenomenon.Co-immunoprecipitation showed that p53 coexisted in a complex with Bat3 and HAUSP in vivo,and HAUSP may serve as a binding mediator to enhance the interaction between p53 and Bat3.Further studies revealed that formation of this three-protein complex interfered with the binding of p53 to its proteasome receptor S5a and promoted the accumulation of p53 in nucleus.Notably,Mdm2 protein abundance is also regulated by Bat3 in the presence of HAUSP.Overexpression of Bat3 and HAUSP increases Mdm2 protein levels without influencing the p53–Mdm2 interaction and Mdm2-mediated p53 ubiquitination,indicating that Bat3–HAUSP-mediated protein stabilization is not specific to p53 and different mechanisms may be involved in Bat3-mediated regulation of p53–Mdm2 pathway.Together,our study unravels a novel mechanism by which p53 is stabilized and activated by HAUSP-mediated interaction with Bat3 and implies that Bat3 might function as a tumor suppressor through the stabilization of p53.

关 键 词：Bat3 p53 stabilization HAUSP S5a proteasome recognition 

分 类 号：Q24[生物学—细胞生物学]