title: Phosphorylation of Tudor-SN, a novel substrate of JNK, is involved in the efficient recruitment of Tudor-SN into stress granules.
abstract: Posttranslational modifications of certain stress granule (SG) proteins are closely related to the assembly of SGs, a type of cytoplasmic foci structure. Our previous studies revealed that the Tudor staphylococcal nuclease (Tudor-SN) protein participates in the formation of SGs. However, the functional significance of potential Tudor-SN modifications during stress has not been reported. In this study, we demonstrated that the Tudor-SN protein was phosphorylated at threonine 103 (T103) upon stimulation with arsenite. In addition, c-Jun N-terminal kinase (JNK) was found to be responsible for Tudor-SN phosphorylation at the T103 site. We further illustrated that either a T103A mutation or the suppression of phosphorylation of T103 by the JNK inhibitor SP600125 inhibited the efficient recruitment of Tudor-SN into SGs. In addition, the T103A mutation could affect the physical binding of Tudor-SN with the G3BP (Ras-GAP SH3 domain-binding protein) protein but not with the HuR (Hu antigen R) protein and AGTR1-3'UTR (3'-untranslated region of angiotensin II receptor, type 1) mRNA cargo. These data suggested that JNK-enhanced Tudor-SN phosphorylation promotes the interaction between Tudor-SN and G3BP and facilitates the efficient recruitment of Tudor-SN into SGs under conditions of sodium arsenite-induced oxidative stress. This finding provides novel insights into the physiological function of Tudor-SN modification.
authors.affiliation: Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin 300070, China; Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Su
authors.affiliation: Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin 300070, China; Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Xingjie
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin 300070, China; Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Wendong
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin 300070, China; Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin 300070, China; Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin 300070, China; Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Xiaoteng
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin 300070, China; Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin 300070, China; Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Lingbiao
authors.initials: L
authors.lastname: Xin
authors.affiliation: Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin 300070, China; Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ren
authors.affiliation: High-throughput Molecular Drug Discovery Center, Tianjin Joint Academy of Biotechnology and Medicine, Tianjin 300457, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Li
authors.affiliation: High-throughput Molecular Drug Discovery Center, Tianjin Joint Academy of Biotechnology and Medicine, Tianjin 300457, China.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Shui
authors.affiliation: Department of Immunology, University of Manitoba, 471 Apotex Centre, 750 McDermot Avenue, Winnipeg R3E 0T5, Canada.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Cardiovascular Surgery, Tianjin Medical University General Hospital, Tianjin 300070, China. Electronic address: minxinw@126.com.
authors.forename: Minxin
authors.initials: M
authors.lastname: Wei
authors.affiliation: Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin 300070, China; Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin 300070, China. Electronic address: yangj@tmu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D018053:Arsenites / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004265:DNA Helicases; D000067780:ELAV-Like Protein 1 / Q000235:genetics / Q000378:metabolism; D004720:Endonucleases; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress; D010766:Phosphorylation / Q000187:drug effects; D000075223:Poly-ADP-Ribose Binding Proteins; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D017670:Sodium Compounds / Q000494:pharmacology; D013912:Threonine / Q000378:metabolism
chemical_list: C544065:AGTR1 protein, human; D000873:Anthracenes; D018053:Arsenites; D002352:Carrier Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D009687:Nuclear Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D047428:Protein Kinase Inhibitors; D000067776:RNA Recognition Motif Proteins; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D017670:Sodium Compounds; C432165:pyrazolanthrone; D013912:Threonine; C017947:sodium arsenite; D048031:JNK Mitogen-Activated Protein Kinases; D004720:Endonucleases; C095221:SND1 protein, human; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases
keywords: C-Jun N-terminal kinase; Phosphorylation; Stress; Stress granules; Tudor-SN