Deubiquitinase JOSD2 stabilizes YAP/TAZ to promote cholangiocarcinoma progression

查看全文 作　　者：Meijia [1]Qian;Fangjie [2]Yan;Weihua [1]Wang;Jiamin [1]Du;Tao [1]Yuan;Ruilin [1]Wu;Chenxi [1]Zhao;Jiao [1]Wang;Jiabin [1]Lu;Bo [3]Zhang;Nengming [3]Lin;Xin [4]Dong;Xiaoyang [1]Dai;Xiaowu [1]Dong;Bo [1]Yang;Hong [1,3,5]Zhu;Qiaojun [1,2,4,5]He

机构地区：[1]Zhejiang Province Key Laboratory of Anti-Cancer Drug Research,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China;[2]Innovation Institute for Artificial Intelligence in Medicine,Zhejiang University,Hangzhou 310058,China;[3]Department of Clinical Pharmacology,Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province,Affiliated Hangzhou First People’s Hospital,Cancer Center,Zhejiang University School of Medicine,Hangzhou 310006,China;[4]Second Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310009,China;[5]Cancer Center of Zhejiang University,Hangzhou 310058,China

出　　处：《Acta Pharmaceutica Sinica B》索引2021年第11卷第12期,共12页

基　　金：supported by the Key Program of the Natural Science Foundation of China(No.81830107);the Natural Science Foundation for Distinguished Young Scholar of China(No.81625024);the Natural Science Foundation of China(No.81773753,No.81973349);the Zhejiang Provincial Natural Science Foundation(No.LR19H310002 and No.LR21H300003,China)。 摘　　要：Cholangiocarcinoma(CCA)has emerged as an intractable cancer with scanty therapeutic regimens.The aberrant activation of Yes-associated protein(YAP)and transcriptional co-activator with PDZ-binding motif(TAZ)are reported to be common in CCA patients.However,the underpinning mechanism remains poorly understood.Deubiquitinase(DUB)is regarded as a main orchestrator in maintaining protein homeostasis.Here,we identified Josephin domain-containing protein 2(JOSD2)as an essential DUB of YAP/TAZ that sustained the protein level through cleavage of polyubiquitin chains in a deubiquitinase activity-dependent manner.The depletion of JOSD2 promoted YAP/TAZ proteasomal degradation and significantly impeded CCA proliferation in vitro and in vivo.Further analysis has highlighted the positive correlation between JOSD2 and YAP abundance in CCA patient samples.Collectively,this study uncovers the regulatory effects of JOSD2 on YAP/TAZ protein stabilities and profiles its contribution in CCA malignant progression,which may provide a potential intervention target for YAP/TAZ-related CCA patients. 关键词：CHOLANGIOCARCINOMA Deubiquitinase JOSD2 YAP/TAZ

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Deubiquitinase JOSD2 stabilizes YAP/TAZ to promote cholangiocarcinoma progression

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