RNF26 temporally regulates virus-triggered type I interferon induction by two distinct mechanisms
Author:  Date:2015-11-20  Clicks:
PLoS Pathog.2014 Sep 25;10(9):e1004358. doi: 10.1371/journal.ppat.1004358. eCollection 2014.

RNF26 temporally regulates virus-triggered typeI interferon induction by two distinct mechanisms.

Qin Y 1, Zhou MT 1, Hu MM 1, Hu YH 1, Zhang J 1, Guo L 1, Zhong B 1, Shu HB 1.

Author information


Viral infection triggersinductionoftypeI interferons (IFNs), which are critical mediators of innate antiviral immune response. Mediator of IRF3 activation (MITA, also called STING) is an adapter essential forvirus-triggeredIFNinductionpathways. How post-translational modifications regulate the activity of MITA is not fully elucidated. In expression screens, we identified RING finger protein 26 (RNF26), an E3 ubiquitin ligase, could mediate polyubiquitination of MITA. Interestingly,RNF26promoted K11-linked polyubiquitination of MITA at lysine 150, a residue also targeted by RNF5 for K48-linked polyubiquitination. Further experiments indicated thatRNF26protected MITA from RNF5-mediated K48-linked polyubiquitination and degradation that was required for quick and efficienttypeI IFN and proinflammatory cytokineinductionafter viral infection. On the other hand,RNF26was required to limit excessivetypeI IFN response but not proinflammatory cytokineinductionby promoting autophagic degradation of IRF3. Consistently, knockdown ofRNF26inhibited the expression of IFNB1 gene in various cells at the early phase and promoted it at the late phase of viral infection, respectively. Furthermore, knockdown ofRNF26inhibited viral replication, indicating thatRNF26antagonizes cellular antiviral response. Our findings thus suggest thatRNF26temporallyregulatesinnate antiviral response bytwodistinctmechanisms.

Tel: 0086-27-68750205 Fax: 0086-27-68759675  Email: mri@whu.edu.cn

Contact address: Donghu Road, No. 115, Wuchang District, Wuhan, Hubei Province, P.R. China. 430071

Copyright @ 2016 Medical Research Institute

XML 地图 | Sitemap 地图