2. Academic Validation
  3. Lysyl Oxidase 3 Is a Dual-Specificity Enzyme Involved in STAT3 Deacetylation and Deacetylimination Modulation

Lysyl Oxidase 3 Is a Dual-Specificity Enzyme Involved in STAT3 Deacetylation and Deacetylimination Modulation

  • Mol Cell. 2017 Jan 19;65(2):296-309. doi: 10.1016/j.molcel.2016.12.002.
Li Ma 1,  Chao Huang 2,  Xiong-Jun Wang 3,  Dazhuan Eric Xin 3,  Li-Shun Wang 3,  Quanli C Zou 3,  Ya-Nan S Zhang 3,  Min-Dian Tan 3,  Yu-Mei Wang 3,  Ting C Zhao 4,  Devasis Chatterjee 4,  Rachel A Altura 4,  Chuangui Wang 5,  Yan S Xu 6,  Jing-Hua Yang 6,  Yong-Sheng Fan 7,  Bao-Hui Han 8,  Jianmin Si 9,  Xiaoren Zhang 3,  Jinke Cheng 10,  Zhijie Chang 11,  Y Eugene Chin 12
Affiliations

Affiliations

  • 1 Institute of Health Sciences, Chinese Academy of Sciences, Jiaotong University School of Medicine, 320 Yueyang Road, Shanghai 200031, China; Departments of Surgery and Medicine, Brown University School of Medicine, Rhode Island Hospital, Providence, RI 02903, USA.
  • 2 Institute of Health Sciences, Chinese Academy of Sciences, Jiaotong University School of Medicine, 320 Yueyang Road, Shanghai 200031, China; Translational Medicine Center, Chest Hospital, Jiaotong University School of Medicine, Shanghai 200030, China. Electronic address: [email protected].
  • 3 Institute of Health Sciences, Chinese Academy of Sciences, Jiaotong University School of Medicine, 320 Yueyang Road, Shanghai 200031, China.
  • 4 Departments of Surgery and Medicine, Brown University School of Medicine, Rhode Island Hospital, Providence, RI 02903, USA.
  • 5 Institute of Biomedical Sciences, East China Normal University, Shanghai 200024, China.
  • 6 Cancer Center, Shandong University School of Medicine, Culture West Street, Jinan, Shandong 250012, China.
  • 7 Department of Immunology, School of Basic Medicine, Zhejiang Chinese Medicine University, Hangzhou, Zhejiang 310053, China.
  • 8 Translational Medicine Center, Chest Hospital, Jiaotong University School of Medicine, Shanghai 200030, China.
  • 9 Clinic Medical Research Institution, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China.
  • 10 Department of Cell Biology and Biochemistry, Jiaotong University School of Medicine, Shanghai 200025, China.
  • 11 State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University School of Medicine, Beijing 100084, China. Electronic address: [email protected].
  • 12 Institute of Health Sciences, Chinese Academy of Sciences, Jiaotong University School of Medicine, 320 Yueyang Road, Shanghai 200031, China. Electronic address: [email protected].
PMID: 28065600 DOI: 10.1016/j.molcel.2016.12.002
Abstract

In mammalian cells, histone deacetylase (HDAC) and Sirtuin (SIRT) are two families responsible for removing acetyl groups from acetylated proteins. Here, we describe protein deacetylation coupled with deacetylimination as a function of lysyl oxidase (LOX) family members. LOX-like 3 (Loxl3) associates with STAT3 in the nucleus to deacetylate and deacetyliminate STAT3 on multiple acetyl-lysine sites. Surprisingly, Loxl3 N-terminal scavenger receptor cysteine-rich (SRCR) repeats, rather than the C-terminal oxidase catalytic domain, represent the major deacetylase/deacetyliminase activity. Loxl3-mediated deacetylation/deacetylimination disrupts STAT3 dimerization, abolishes STAT3 transcription activity, and restricts cell proliferation. In Loxl3-/- mice, STAT3 is constitutively acetylated and naive CD4+ T cells are potentiated in Th17/Treg cell differentiation. When overexpressed, the SRCR repeats from other LOX family members can catalyze protein deacetylation/deacetylimination. Thus, our findings delineate a hitherto-unknown mechanism of protein deacetylation and deacetylimination catalyzed by lysyl oxidases.

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