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Dev Comp Immunol. 2014 Mar;43(1):23-9. doi: 10.1016/j.dci.2013.10.007. Epub 2013 Oct 29.

Conserved inhibitory role of teleost SOCS-1s in IFN signaling pathways.

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  • 1College 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.
  • 2College 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.
  • 3College 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.

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.

Copyright © 2013 Elsevier Ltd. All rights reserved.

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

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