title: MDA5 is SUMOylated by PIAS2β in the upregulation of type I interferon signaling.
abstract: Retinoic acid-inducible protein I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are cytosolic viral RNA sensors that induce type I interferon production (IFN). In this study, we found that MDA5 undergoes inducible SUMOylation by small ubiquitin-like modifier-1 (SUMO-1) in response to polyI:C stimulation. Enhanced SUMOylation of MDA5 by exogenously expressed SUMO-conjugating enzyme Ubc9 correlated with upregulation of IFN expression and repressed virus replication. Conversely, overexpression of a SUMOylation-deficient mutant of Ubc9 or knockdown of endogenous Ubc9 reduced IFN production. Furthermore, we showed that PIAS2β, a SUMOylation E3 ligase, could specifically interact with and enhance the SUMOylation of MDA5. Consequently, PIAS2β knockdown reduced the SUMOylation of MDA5 and the IFN production. Collectively, these findings suggest that SUMO-1 modification of MDA5 possibly via PIAS2β may play a role in the MDA5-mediated IFN response to viral infections.
authors.affiliation: Key Laboratory of Infection and Immunity of Chinese Academy of Sciences, the Institute of Biophysics, 15 Da Tun Road, Chaoyang District, Beijing 100101, China.
authors.forename: Jihuan
authors.initials: J
authors.lastname: Fu
authors.forename: Yanbao
authors.initials: Y
authors.lastname: Xiong
authors.forename: Youli
authors.initials: Y
authors.lastname: Xu
authors.forename: Genhong
authors.initials: G
authors.lastname: Cheng
authors.forename: Hong
authors.initials: H
authors.lastname: Tang
mesh_terms: D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D000072640:Interferon-Induced Helicase, IFIH1; D011070:Poly I-C / Q000378:metabolism; D011485:Protein Binding; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism*; D015398:Signal Transduction; D058207:Sumoylation; D054875:Ubiquitination; D015854:Up-Regulation
chemical_list: D007370:Interferon Type I; C501001:PIAS2 protein, human; D050828:Protein Inhibitors of Activated STAT; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D011070:Poly I-C