title: GdX/UBL4A specifically stabilizes the TC45/STAT3 association and promotes dephosphorylation of STAT3 to repress tumorigenesis.
abstract: Impaired phosphatase activity contributes to the persistent activation of STAT3 in tumors. Given that STAT family members with various or even opposite functions are often phosphorylated or dephosphorylated by the same enzymes, the mechanism for STAT3-specific dephosphorylation in cells remains largely unknown. Here, we report that GdX (UBL4A) promotes STAT3 dephosphorylation via mediating the interaction between TC45 (the nuclear isoform of TC-PTP) and STAT3 specifically. GdX stabilizes the TC45-STAT3 complex to bestow upon STAT3 an efficient dephosphorylation by TC45. Inasmuch, GdX suppresses tumorigenesis and tumor development by reducing the level of phospho-STAT3 (p-STAT3), whereas deletion of GdX results in a high level of p-STAT3 and accelerated colorectal tumorigenesis induced by AOM/DSS. Thus, GdX converts TC45, a nonspecific phosphatase, into a STAT3-specific phosphatase by bridging an association between TC45 and STAT3.
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China.
authors: Yangmeng
authors: Y
authors: Wang
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China; Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors: Hongxiu
authors: H
authors: Ning
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China.
authors: Fangli
authors: F
authors: Ren
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China.
authors: Yuanjiang
authors: Y
authors: Zhang
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China.
authors: Yu
authors: Y
authors: Rong
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China.
authors: Yinyin
authors: Y
authors: Wang
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China.
authors: Fuqin
authors: F
authors: Su
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China.
authors: Chenguang
authors: C
authors: Cai
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China.
authors: Zhe
authors: Z
authors: Jin
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China.
authors: Zhiyong
authors: Z
authors: Li
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China.
authors: Xinqi
authors: X
authors: Gong
authors: Beijing Key Lab, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
authors: Yonggong
authors: Y
authors: Zhai
authors: Departments of General Surgery and Pathology, Chinese PLA General Hospital, Beijing 100853, China.
authors: Dianjun
authors: D
authors: Wang
authors: Departments of General Surgery and Pathology, Chinese PLA General Hospital, Beijing 100853, China.
authors: Baoqing
authors: B
authors: Jia
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China.
authors: Ying
authors: Y
authors: Qiu
authors: Department of Pathology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan.
authors: Yasuhiko
authors: Y
authors: Tomita
authors: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease and Li Ka Shing Institute of Health Sciences, the Chinese University of Hong Kong, Hong Kong, China.
authors: Joseph J Y
authors: JJ
authors: Sung
authors: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease and Li Ka Shing Institute of Health Sciences, the Chinese University of Hong Kong, Hong Kong, China.
authors: Jun
authors: J
authors: Yu
authors: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors: David M
authors: DM
authors: Irwin
authors: State Key Laboratory of Proteomics, Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing 100071, China.
authors: Xiao
authors: X
authors: Yang
authors: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
authors: Xinyuan
authors: X
authors: Fu
authors: Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. Electronic address: yechin@sibs.ac.cn.
authors: Y Eugene
authors: YE
authors: Chin
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China. Electronic address: zhijiec@tsinghua.edu.cn.
authors: Zhijie
authors: Z
authors: Chang
mesh_terms: D000818:Animals; D019556:COS Cells; D063646:Carcinogenesis; D002471:Cell Transformation, Neoplastic; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D008546:Melanoma, Experimental; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D011485:Protein Binding; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000737:chemistry*; D050796:STAT3 Transcription Factor / Q000737:chemistry*; D014452:Ubiquitins / Q000737:chemistry* / Q000235:genetics
chemical_list: D016207:Cytokines; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D014452:Ubiquitins; C583268:Ubl4A protein, human; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2