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Deubiquitinase JOSD2 stabilizes YAP/TAZ to promote cholangiocarcinoma progression

Acta Pharm Sin B. 2021-06; 
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
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Proteins, Expression, Isolation and Analysis … beads (#L00425), anti-HA magnetic beads (#B26202) and SureBeads™ Protein G (#161-4023) for immunoprecipitation (IP) were obtained from GenScript (Nanjing, China), Biomake … Get A Quote

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 C... More

关键词

CCA, cholangiocarcinoma, Cholangiocarcinoma, DAB, 3,3-diaminobenzidine tetrahydrochloride chromogen, DUB, deubiquitinase, Deubiquitinase, FGFR, fibroblast growth factor receptor, FOLFOX, folinic acid, 5-FU and oxaliplatin, IDH1/2, isocitrate dehydrogenase 1/2, IHC, immunohistochemistry, IP, immunoprecipitation, JOSD2, KRAS, kirsten rat sarcoma 2 viral oncogene homolog, LATS1/2, large tumor suppressor kinase 1/2, MST1/2, mammalian Ste20-like kinases 1/2, OTUB2, otubain-2, PBS, phosphate-buffered saline, PDC, patient derived cell, PDX, patient-derived xenograft, RTV, relative tumor volume, SRB, sulforhodamine B, TAZ, transcriptional co-activator with PDZ-binding motif, TCGA, The Cancer Genome Atlas, USP9X/10/47, ubiquitin-specific peptidase 9X/10/47, YAP, Yes-associated protein, YAP/TAZ, YOD1, ubiquitin thioesterase OTU1, rhJOSD2, recombinant human JOSD2, shRNA, specific hairpin RNA