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The tumour suppressor CYLD is a negative regulator of RIG‐I‐mediated antiviral response
Author(s) -
Friedman Constantin S,
O'Donnell Marie Anne,
LegardaAddison Diana,
Ng Aylwin,
Cárdenas Washington B,
Yount Jacob S,
Moran Thomas M,
Basler Christopher F,
Komuro Akihiko,
Horvath Curt M,
Xavier Ramnik,
Ting Adrian T
Publication year - 2008
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2008.136
Subject(s) - irf3 , rig i , tank binding kinase 1 , biology , deubiquitinating enzyme , rna helicase a , gene knockdown , interferon regulatory factors , interferon , ectopic expression , transcription factor , microbiology and biotechnology , irf7 , irf1 , interferon type i , signal transduction , kinase , gene , protein kinase a , rna , ubiquitin , helicase , genetics , map kinase kinase kinase
On detecting viral RNAs, the RNA helicase retinoic acid‐inducible gene I (RIG‐I) activates the interferon regulatory factor 3 (IRF3) signalling pathway to induce type I interferon (IFN) gene transcription. How this antiviral signalling pathway might be negatively regulated is poorly understood. Microarray and bioinformatic analysis indicated that the expression of RIG‐I and that of the tumour suppressor CYLD (cylindromatosis), a deubiquitinating enzyme that removes Lys 63‐linked polyubiquitin chains, are closely correlated, suggesting a functional association between the two molecules. Ectopic expression of CYLD inhibits the IRF3 signalling pathway and IFN production triggered by RIG‐I; conversely, CYLD knockdown enhances the response. CYLD removes polyubiquitin chains from RIG‐I as well as from TANK binding kinase 1 (TBK1), the kinase that phosphorylates IRF3, coincident with an inhibition of the IRF3 signalling pathway. Furthermore, CYLD protein level is reduced in the presence of tumour necrosis factor and viral infection, concomitant with enhanced IFN production. These findings show that CYLD is a negative regulator of RIG‐I‐mediated innate antiviral response.