Sep 26, 2014

RNF26 temporally regulates virus-triggered type I interferon induction by two distinct mechanisms

PLoS Pathogens
Yue QinHong-Bing Shu

Abstract

Viral infection triggers induction of type I interferons (IFNs), which are critical mediators of innate antiviral immune response. Mediator of IRF3 activation (MITA, also called STING) is an adapter essential for virus-triggered IFN induction pathways. 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, RNF26 promoted K11-linked polyubiquitination of MITA at lysine 150, a residue also targeted by RNF5 for K48-linked polyubiquitination. Further experiments indicated that RNF26 protected MITA from RNF5-mediated K48-linked polyubiquitination and degradation that was required for quick and efficient type I IFN and proinflammatory cytokine induction after viral infection. On the other hand, RNF26 was required to limit excessive type I IFN response but not proinflammatory cytokine induction by promoting autophagic degradation of IRF3. Consistently, knockdown of RNF26 inhibited 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 of RNF26 inhibite...Continue Reading

Mentioned in this Paper

Pathologic Cytolysis
Establishment and Maintenance of Localization
Real-Time Polymerase Chain Reaction
Polyubiquitination
Immune Response
Biochemical Pathway
Amidophosphoribosyltransferase
IkappaB Kinase Activity
Lysosome Assembly Pathway
Transfection

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