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

• 来源期刊: 分子细胞生物学报（英文版）
• 年，卷（期）: 2011,（5）
• 页码范围: 283-292
• 页数: 10页
• 语种: 中文
• DOI: 10.1093/imcb/mjr020

摘要

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 iysines 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.