1.Deubiquitinase JOSD2 stabilizes YAP/TAZ to promote cholangiocarcinoma progression.
Meijia QIAN ; Fangjie YAN ; Weihua WANG ; Jiamin DU ; Tao YUAN ; Ruilin WU ; Chenxi ZHAO ; Jiao WANG ; Jiabin LU ; Bo ZHANG ; Nengming LIN ; Xin DONG ; Xiaoyang DAI ; Xiaowu DONG ; Bo YANG ; Hong ZHU ; Qiaojun HE
Acta Pharmaceutica Sinica B 2021;11(12):4008-4019
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
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