title: Conserved inhibitory role of teleost SOCS-1s in IFN signaling pathways.
abstract: The suppressor of cytokine signaling 1 (SOCS-1) protein is a critical regulator in the immune systems of humans and mammals, which functions classically as an inhibitor of the IFN signaling pathways. However, data on functional characterisation of SOCS-1 in ancient vertebrates are limited. In this study, we report the function of teleost SOCS-1s in IFN signaling in fish models (zebrafish and Tetraodon) and human cells. Structurally, teleost SOCS-1s share conserved functional domains with their mammalian counterparts. Functionally, teleost SOCS-1s could be significantly induced upon stimulation with IFN stimulants and zebrafish IFNφ1. Overexpression of teleost SOCS-1s could dramatically suppress IFNφ1-induced Mx, Viperin and PKZ activation in zebrafish, and IFN-induced ISG15 activation in HeLa cells. Furthermore, a SOCS-1 variant that lacks the KIR domain was also characterised. This study demonstrates the conserved negative regulatory role of teleost SOCS-1s in IFN signaling pathways, providing perspective into the functional conservation of SOCS-1 proteins during evolution.
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou 310058, People's Republic of China; Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Hangzhou 310058, People's Republic of China; Key Laboratory of Animal Virology of Ministry of Agriculture, Hangzhou 310058, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Nie
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou 310058, People's Republic of China; Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Hangzhou 310058, People's Republic of China; Key Laboratory of Animal Virology of Ministry of Agriculture, Hangzhou 310058, People's Republic of China.
authors.forename: Ran
authors.initials: R
authors.lastname: Xiong
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou 310058, People's Republic of China; Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Hangzhou 310058, People's Republic of China; Key Laboratory of Animal Virology of Ministry of Agriculture, Hangzhou 310058, People's Republic of China.
authors.forename: Ying-Sheng
authors.initials: YS
authors.lastname: Zhang
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou 310058, People's Republic of China; Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Hangzhou 310058, People's Republic of China; Key Laboratory of Animal Virology of Ministry of Agriculture, Hangzhou 310058, People's Republic of China.
authors.forename: Lv-yun
authors.initials: LY
authors.lastname: Zhu
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou 310058, People's Republic of China; Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Hangzhou 310058, People's Republic of China; Key Laboratory of Animal Virology of Ministry of Agriculture, Hangzhou 310058, People's Republic of China. Electronic address: shaojz@zju.edu.cn.
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Shao
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou 310058, People's Republic of China; Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Hangzhou 310058, People's Republic of China; Key Laboratory of Animal Virology of Ministry of Agriculture, Hangzhou 310058, People's Republic of China. Electronic address: xianglx@zju.edu.cn.
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Xiang
mesh_terms: D000818:Animals; D017124:Conserved Sequence; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism*; D014644:Genetic Variation; D006367:HeLa Cells; D006801:Humans; D007372:Interferons / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008322:Mammals; D009154:Mutation / Q000235:genetics; D064547:Myxovirus Resistance Proteins / Q000235:genetics / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D023721:Tetraodontiformes / Q000276:immunology*; D019076:Transgenes / Q000235:genetics; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000276:immunology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D029941:Fish Proteins; D047908:Intracellular Signaling Peptides and Proteins; D064547:Myxovirus Resistance Proteins; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014452:Ubiquitins; D029961:Zebrafish Proteins; C540939:socs1a protein, zebrafish; C074034:ISG15 protein, human; D007372:Interferons; C583881:PKZ protein, zebrafish; D011494:Protein Kinases
keywords: CISH; DMEM; Danio rerio IFNφ1; Danio rerio MAVS; Danio rerio SOCS-1; DrIFNφ1; DrMAVS; DrSOCS-1; Dulbecco’s modified Eagle’s medium; IFN; IFN signal pathway; IFN-I; IFN-stimulated genes; ISG; JAK-STAT; MAVS; MDA5; Negative regulator; PKZ; RIG-I; RIG-I-like receptors; RLRs; SOCS-1; SOCS-1 variant; TLR-3; Teleost fish SOCS-1; Tetraodon nigroviridis SOCS-1; TnSOCS-1; cytokine-inducible SH2-domain containing protein; interferon; melanoma differentiation-associated gene-5; mitochondrial antiviral signaling protein; poly(I:C); polyinosinic–polycytidylic acid; protein kinase containing Z-DNA binding domains; retinoic acid-inducible gene I; suppressor of cytokine signaling 1; the Janus kinase signal transducer and activator of transcription; toll-like receptor 3; type I IFN