title: Lysyl Oxidase 3 Is a Dual-Specificity Enzyme Involved in STAT3 Deacetylation and Deacetylimination Modulation.
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.
authors.affiliation: 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.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: 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: c_huang_bio@msn.com.
authors.forename: Chao
authors.initials: C
authors.lastname: Huang
authors.affiliation: Institute of Health Sciences, Chinese Academy of Sciences, Jiaotong University School of Medicine, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Xiong-Jun
authors.initials: XJ
authors.lastname: Wang
authors.affiliation: Institute of Health Sciences, Chinese Academy of Sciences, Jiaotong University School of Medicine, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Dazhuan Eric
authors.initials: DE
authors.lastname: Xin
authors.affiliation: Institute of Health Sciences, Chinese Academy of Sciences, Jiaotong University School of Medicine, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Li-Shun
authors.initials: LS
authors.lastname: Wang
authors.affiliation: Institute of Health Sciences, Chinese Academy of Sciences, Jiaotong University School of Medicine, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Quanli C
authors.initials: QC
authors.lastname: Zou
authors.affiliation: Institute of Health Sciences, Chinese Academy of Sciences, Jiaotong University School of Medicine, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Ya-Nan S
authors.initials: YS
authors.lastname: Zhang
authors.affiliation: Institute of Health Sciences, Chinese Academy of Sciences, Jiaotong University School of Medicine, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Min-Dian
authors.initials: MD
authors.lastname: Tan
authors.affiliation: Institute of Health Sciences, Chinese Academy of Sciences, Jiaotong University School of Medicine, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Wang
authors.affiliation: Departments of Surgery and Medicine, Brown University School of Medicine, Rhode Island Hospital, Providence, RI 02903, USA.
authors.forename: Ting C
authors.initials: TC
authors.lastname: Zhao
authors.affiliation: Departments of Surgery and Medicine, Brown University School of Medicine, Rhode Island Hospital, Providence, RI 02903, USA.
authors.forename: Devasis
authors.initials: D
authors.lastname: Chatterjee
authors.affiliation: Departments of Surgery and Medicine, Brown University School of Medicine, Rhode Island Hospital, Providence, RI 02903, USA.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Altura
authors.affiliation: Institute of Biomedical Sciences, East China Normal University, Shanghai 200024, China.
authors.forename: Chuangui
authors.initials: C
authors.lastname: Wang
authors.affiliation: Cancer Center, Shandong University School of Medicine, Culture West Street, Jinan, Shandong 250012, China.
authors.forename: Yan S
authors.initials: YS
authors.lastname: Xu
authors.affiliation: Cancer Center, Shandong University School of Medicine, Culture West Street, Jinan, Shandong 250012, China.
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Yang
authors.affiliation: Department of Immunology, School of Basic Medicine, Zhejiang Chinese Medicine University, Hangzhou, Zhejiang 310053, China.
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Fan
authors.affiliation: Translational Medicine Center, Chest Hospital, Jiaotong University School of Medicine, Shanghai 200030, China.
authors.forename: Bao-Hui
authors.initials: BH
authors.lastname: Han
authors.affiliation: Clinic Medical Research Institution, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Si
authors.affiliation: Institute of Health Sciences, Chinese Academy of Sciences, Jiaotong University School of Medicine, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Xiaoren
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology and Biochemistry, Jiaotong University School of Medicine, Shanghai 200025, China.
authors.forename: Jinke
authors.initials: J
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University School of Medicine, Beijing 100084, China. Electronic address: zhijiec@tsinghua.edu.cn.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Chang
authors.affiliation: Institute of Health Sciences, Chinese Academy of Sciences, Jiaotong University School of Medicine, 320 Yueyang Road, Shanghai 200031, China. Electronic address: yechin@sibs.ac.cn.
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Chin
mesh_terms: D000107:Acetylation; D000594:Amino Acid Oxidoreductases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D002384:Catalysis; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000201:enzymology; D049109:Cell Proliferation; D003092:Colitis / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005838:Genotype; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D000072417:Protein Domains; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000201:enzymology / Q000276:immunology; D058504:Th17 Cells / Q000201:enzymology / Q000276:immunology; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D000594:Amino Acid Oxidoreductases; C435668:LOXL3 protein, human; C511777:LOXL3 protein, mouse