Ankrd17 positively regulates RIG-I-like receptor (RLR)-mediated immune signaling.
Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), such as RIG-I, melanoma differentiation-associated gene 5 (MDA5), and virus-induced signaling adaptor (VISA), are intracellular molecules that sense diverse viral RNAs and trigger immune responses. In this study, we demonstrate that the ankyrin repeat protein ankrd17 interacts with RIG-I, MDA5, and VISA and upregulates RLR-mediated immune signaling. Overexpression of ankrd17 enhances RLR-mediated activation of IRF-3 and NF-κB and upregulates the transcription of IFN-β. It also promotes RLR signaling in response to poly (I:C), influenza virus RNA, and Sendai virus. Consistently, knockdown of ankrd17 impairs RLR signaling. Furthermore, we demonstrate that ankrd17 enhances the interaction of RIG-I and MDA5 with VISA; the ankyrin repeat domain of ankrd17 is required for its interaction with RIG-I as well as for its function in regulating the RLR pathway. Taken together, our results indicate that ankrd17 is a positive regulator of the RLR signaling pathway.
Center for Molecular Immunology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P R China.
Yetao
Y
Wang
Xiaomei
X
Tong
Gang
G
Li
Junhui
J
Li
Min
M
Deng
Xin
X
Ye
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000276:immunology; D017089:Ankyrin Repeat / Q000276:immunology; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D055785:Gene Knockdown Techniques; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000276:immunology; D000072640:Interferon-Induced Helicase, IFIH1; D016899:Interferon-beta / Q000096:biosynthesis / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D009975:Orthomyxoviridae / Q000276:immunology; D011070:Poly I-C / Q000276:immunology; D012367:RNA, Viral / Q000276:immunology; D016601:RNA-Binding Proteins; D011971:Receptors, Immunologic; D029082:Sendai virus / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
C481273:ANKRD17 protein, human; D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; C505371:MAVS protein, human; D016328:NF-kappa B; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D011971:Receptors, Immunologic; D016899:Interferon-beta; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D011070:Poly I-C