SENP2 negatively regulates cellular antiviral response by deSUMOylating IRF3 and conditioning it for ubiquitination and degradation

Yong Ran, Tian Tian Liu, Qian Zhou, Shu Li, Ai Ping Mao, Ying Li, Li Juan Liu, Jin Ke Cheng, Hong Bing Shu

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

Transcription factor IRF3-mediated type I interferon induction is essential for antiviral innate immunity. We identified the deSUMOylating enzyme Sentrin/SUMO-specific protease (SENP) 2 as a negative regulator of virus-triggered IFN-β induction. Overexpression of SENP2 caused IRF3 deSUMOylation, K48-linked ubiquitination, and degradation, whereas depletion of SENP2 had opposite effects. Both the SUMOylation and K48-linked ubiquitination of IRF3 occurred at lysines 70 and 87, and these processes are competitive. The level of virus-triggered IFN-β was markedly up-regulated and viral replication was reduced in SENP2-deficient cells comparing with wild-type controls. Our findings suggest that SENP2 regulates antiviral innate immunity by deSUMOylating IRF3 and conditioning it for ubiquitination and degradation, and provide an example of cross-talk between the ubiquitin and SUMO pathways in innate immunity.

Original languageEnglish
Pages (from-to)283-292
Number of pages10
JournalJournal of Molecular Cell Biology
Volume3
Issue number5
DOIs
StatePublished - Oct 2011

Keywords

  • deSUMOylation
  • innate immunity
  • IRF3
  • SENP2
  • ubiquitination

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