The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response

Constantin S. Friedman, Marie Anne O'Donnell, Diana Legarda-Addison, Aylwin Ng, Washington B. Cárdenas, Jacob S. Yount, Thomas M. Moran, Christopher F. Basler, Akihiko Komuro, Curt M. Horvath, Ramnik Xavier, Adrian T. Ting

Research output: Contribution to journalArticlepeer-review

232 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)930-936
Number of pages7
JournalEMBO Reports
Volume9
Issue number9
DOIs
StatePublished - 2008

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response'. Together they form a unique fingerprint.

Cite this