RAD23A negatively regulates RIG-I/MDA5 signaling through promoting TRAF2 polyubiquitination and degradation.
RIG-I/MDA5 plays a pivotal role in innate immunity by detecting intracellular double-stranded RNA (dsRNA) and activating the transcription of type I interferons and proinflammatory factors, but the exactly regulating mechanism of RIG-I/MDA5 signaling remains elusive. In this study, UbL-UBA domain containing protein RAD23A was identified as a negative regulator of RIG-I/MDA5-mediated signaling activation through a small interfering RNA (siRNA)-based screening. Knockdown of RAD23A augmented the expression of RIG-I/MDA5-mediated expression of proinflammatory cytokines and IFN-β whereas ectopic expression of RAD23A showed the converse effect. Moreover, we confirmed the interaction between RAD23A and tumor necrosis factor receptor-associated factor 2 (TRAF2), an essential mediator of RIG-I/MDA5 signaling, and found that RAD23A down-regulated TRAF2 protein level through ubiquitin-proteasome system. Therefore, this study identified RAD23A as a novel negative regulator of RIG-I/MDA5 mediated anti-virus response.
Cancer Center, The First Hospital, Jilin University, Changchun 130021, PR China.
Di-Feng
DF
Fang
Kun
K
He
Jie
J
Wang
Rui
R
Mu
Bo
B
Tan
Zhao
Z
Jian
Hui-Yan
HY
Li
Wei
W
Song
Yan
Y
Chang
Wei-Li
WL
Gong
Wei-Hua
WH
Li
Guan-Jun
GJ
Wang
D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D004279:DNA, Viral / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D016899:Interferon-beta / Q000096:biosynthesis; D016328:NF-kappa B / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D034741:RNA, Small Interfering / Q000235:genetics; D012367:RNA, Viral / Q000276:immunology; D011971:Receptors, Immunologic; D015398:Signal Transduction; D047992:TNF Receptor-Associated Factor 2 / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination
D004279:DNA, Viral; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D034741:RNA, Small Interfering; D012367:RNA, Viral; D011971:Receptors, Immunologic; D047992:TNF Receptor-Associated Factor 2; D025801:Ubiquitin; C086985:RAD23A protein, human; D016899:Interferon-beta; D046988:Proteasome Endopeptidase Complex; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D045643:DNA Repair Enzymes