文献类型：期刊文献

英文题名：Phosphorylation enhanced OTUD3 deubiquitination ARID3A promotes the progress of cholangiocarcinoma

作者：Zhang, Deng-Yong[1];Zhu, Yan[2];Ma, Shuo-Shuo[1,3];Xu, Chen-yang[4];Wang, Zhong-Lin[5];Wang, Hui[4];Liu, Si-hua[1];Shang, Jin[3];Huang, Xiao-Lun[3];Malgulwar, Prit Benny[2];Chen, Fang-fang[1];Zhao, Wei-ying[4];Lu, Zheng[1]

机构：[1]Bengbu Med Univ, Affiliated Hosp 1, Dept Gen Surg, Bengbu, Anhui, Peoples R China;[2]Yangzhou Univ, Coll Anim Sci & Technol, Yangzhou, Jiangsu, Peoples R China;[3]Univ Elect Sci & Technol China, Sichuan Canc Hosp & Inst, Liver Transplantat Ctr & HBP Surg, Chengdu, Peoples R China;[4]Shaoxing Univ, Med Coll, Shaoxing, Peoples R China;[5]Tsinghua Univ, Sch Publ Policy & Management, Beijing, Peoples R China

年份：2025

外文期刊名：ONCOGENE

收录：SCI-EXPANDED(收录号：WOS:001459035200001)、、Scopus(收录号：2-s2.0-105001865243)、WOS

基金：This study was supported by Anhui province health scientific research project (AHWJ2023b015), Anhui Provincial Natural Science Foundation (202308085MH271), Anhui University Natural Science Research Project (2024AH051282), the sixth batch of "special support plan" leading talent projects in Anhui Province.

语种：英文

外文摘要：Cholangiocarcinoma (CCA) is a highly heterogeneous group of malignant tumors with different molecular etiologies and clinical manifestations. Post-translational modifications (PTM) such as ubiquitination and phosphorylation are widely involved in the progression of CCA. Our aim was to elucidate the effect of the deubiquitinating enzyme OTU domain-containing protein 3 (OTUD3) on the molecular pathogenesis of CAA. OTUD3 and ARID3A exhibit direct binding interactions and cytosolic substructural co-localization in CCA cells.OTUD3 specifically removes the ARID3A proteins K240 and K329 OTUD3 specifically removes the ubiquitinated chains at K240 and K329 of ARID3A protein, thereby enhancing ARID3A stability. OTUD3 promotes CCA proliferation and metastasis in vivo and in vitro by interacting with ARID3A.GSK3 beta interacts with OTUD3 protein and mediates phosphorylation of the Ser9 site of OTUD3, which enhances the affinity of OTUD3 to ARID3A and further stabilizes ARID3A protein. The expression of OTUD3 and ARID3A in CCA tissues is highly correlated, and the high expression of both proteins is closely related to the poor prognosis of patients. In conclusion, GSK3 beta phosphorylates OTUD3, enhances its binding ability to ARID3A, and ultimately inhibits the ubiquitination degradation of ARID3A, which promotes the progression of CCA. The GSK3 beta-OTUD3-ARID3A signaling pathway has been demonstrated for the first time in the progression of CCA.