Stabilization of Pin1 by USP34 promotes Ubc9 isomerization and protein sumoylation in glioma stem cells

作者全名："Zhu, Qiuhong; Liang, Panpan; Meng, Hao; Li, Fangzhen; Miao, Wei; Chu, Cuiying; Wang, Wei; Li, Dongxue; Chen, Cong; Shi, Yu; Yu, Xingjiang; Ping, Yifang; Niu, Chaoshi; Wu, Hai-bo; Zhang, Aili; Bian, Xiu-wu; Zhou, Wenchao"

作者地址："[Zhu, Qiuhong; Liang, Panpan; Meng, Hao; Li, Fangzhen; Miao, Wei; Chu, Cuiying; Wang, Wei; Wu, Hai-bo; Zhou, Wenchao] Univ Sci & Technol China, Affiliated Hosp USTC 1, Dept Pathol, Div Life Sci & Med, Hefei, Anhui, Peoples R China; [Zhu, Qiuhong; Liang, Panpan; Meng, Hao; Li, Fangzhen; Miao, Wei; Chu, Cuiying; Wang, Wei; Li, Dongxue; Chen, Cong; Ping, Yifang; Wu, Hai-bo; Bian, Xiu-wu; Zhou, Wenchao] Univ Sci & Technol China, Affiliated Hosp USTC 1, Intelligent Pathol Inst, Div Life Sci & Med, Hefei, Anhui, Peoples R China; [Li, Dongxue; Niu, Chaoshi] Univ Sci & Technol China, Affiliated Hosp USTC 1, Dept Neurosurg, Div Life Sci & Med, Hefei, Peoples R China; [Chen, Cong; Shi, Yu; Ping, Yifang; Bian, Xiu-wu] Third Mil Med Univ, Southwest Hosp, Inst Pathol & Southwest Canc Ctr, Army Med Univ, Chongqing, Peoples R China; [Chen, Cong; Shi, Yu; Ping, Yifang; Bian, Xiu-wu] Minist Educ China, Key Lab Tumor Immunopathol, Chongqing, Peoples R China; [Yu, Xingjiang] Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Basic Med, Dept Histol & Embryol, Wuhan, Peoples R China; [Zhang, Aili] Anhui Med Univ, Sch Life Sci, Dept Cell Biol, Hefei, Anhui, Peoples R China"

通信作者："Zhou, WC (通讯作者)，Univ Sci & Technol China, Affiliated Hosp USTC 1, Dept Pathol, Div Life Sci & Med, Hefei, Anhui, Peoples R China.; Bian, XW; Zhou, WC (通讯作者)，Univ Sci & Technol China, Affiliated Hosp USTC 1, Intelligent Pathol Inst, Div Life Sci & Med, Hefei, Anhui, Peoples R China.; Bian, XW (通讯作者)，Third Mil Med Univ, Southwest Hosp, Inst Pathol & Southwest Canc Ctr, Army Med Univ, Chongqing, Peoples R China.; Bian, XW (通讯作者)，Minist Educ China, Key Lab Tumor Immunopathol, Chongqing, Peoples R China.; Zhang, AL (通讯作者)，Anhui Med Univ, Sch Life Sci, Dept Cell Biol, Hefei, Anhui, Peoples R China."

来源：NATURE COMMUNICATIONS

ESI学科分类：　

WOS号：WOS:001158425400046

JCR分区：Q1

影响因子：16.6

年份：2024

卷号：15

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："The peptidyl-prolyl cis-trans isomerase Pin1 is a pivotal therapeutic target in cancers, but the regulation of Pin1 protein stability is largely unknown. High Pin1 expression is associated with SUMO1-modified protein hypersumoylation in glioma stem cells (GSCs), but the underlying mechanisms remain elusive. Here we demonstrate that Pin1 is deubiquitinated and stabilized by USP34, which promotes isomerization of the sole SUMO E2 enzyme Ubc9, leading to SUMO1-modified hypersumoylation to support GSC maintenance. Pin1 interacts with USP34, a deubiquitinase with preferential expression and oncogenic function in GSCs. Such interaction is facilitated by Plk1-mediated phosphorylation of Pin1. Disruption of USP34 or inhibition of Plk1 promotes polyubiquitination and degradation of Pin1. Furthermore, Pin1 isomerizesUbc9 to upregulate Ubc9 thioester formation with SUMO1, which requires CDK1mediated phosphorylation of Ubc9. Combined inhibition of Pin1 and CDK1 with sulfopin and RO3306 most effectively suppresses orthotopic tumor growth. Our findings provide multiple molecular targets to induce Pin1 degradation and suppress hypersumoylation for cancer treatment."

基金机构："National Natural Science Foundation of China [82373087, 81972782, 82173354]; Anhui Provincial Natural Science Foundation [1908085MH283, 2108085J43]; Key Laboratory of Tumor Immunology and Pathology (Army Medical University), Ministry of Education [2021jsz709]"

基金资助正文："We thank Dr. Jeremy N. Rich for kindly providing the cells used in this study. We are grateful to the core facilities at the University of Science and Technology of China (USTC) and the First Affiliated Hospital of USTC for their assistance in flowcytometry and microscopy. This work was supported by the National Natural Science Foundation of China grants Nos. 81972782 and 82173354 (W.Z.), the Anhui Provincial Natural Science Foundation grant No. 2108085J43 (W.Z.), the National Natural Science Foundation of China grant No. 82373087 (A.Z.), the Anhui Provincial Natural Science Foundation grant No. 1908085MH283 (D.L.), and the Key Laboratory of Tumor Immunology and Pathology (Army Medical University), Ministry of Education grant No. 2021jsz709 (D.L.)."