RRC ID 52295
Author Hayakawa S, Shiratori S, Yamato H, Kameyama T, Kitatsuji C, Kashigi F, Goto S, Kameoka S, Fujikura D, Yamada T, Mizutani T, Kazumata M, Sato M, Tanaka J, Asaka M, Ohba Y, Miyazaki T, Imamura M, Takaoka A.
Title ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I during antiviral responses.
Journal Nat. Immunol.
Abstract The poly(ADP-ribose) polymerases (PARPs) participate in many biological and pathological processes. Here we report that the PARP-13 shorter isoform (ZAPS), rather than the full-length protein (ZAP), was selectively induced by 5'-triphosphate-modified RNA (3pRNA) and functioned as a potent stimulator of interferon responses in human cells mediated by the RNA helicase RIG-I. ZAPS associated with RIG-I to promote the oligomerization and ATPase activity of RIG-I, which led to robust activation of IRF3 and NF-κB transcription factors. Disruption of the gene encoding ZAPS resulted in impaired induction of interferon-α (IFN-α), IFN-β and other cytokines after viral infection. These results indicate that ZAPS is a key regulator of RIG-I signaling during the innate antiviral immune response, which suggests its possible use as a therapeutic target for viral control.
Volume 12(1)
Pages 37-44
Published 2011-1
DOI 10.1038/ni.1963
PII ni.1963
PMID 21102435
MeSH Avulavirus Infections / immunology Avulavirus Infections / metabolism* DEAD Box Protein 58 DEAD-box RNA Helicases / immunology DEAD-box RNA Helicases / metabolism* Gene Expression Regulation / genetics Gene Expression Regulation / immunology HEK293 Cells Humans Immunity, Innate Interferon Type I / genetics Interferon Type I / metabolism Newcastle disease virus / pathogenicity Newcastle disease virus / physiology* Orthomyxoviridae / pathogenicity Orthomyxoviridae / physiology* Orthomyxoviridae Infections / immunology Orthomyxoviridae Infections / metabolism* Poly I-C / immunology Poly(ADP-ribose) Polymerases / genetics Poly(ADP-ribose) Polymerases / immunology Poly(ADP-ribose) Polymerases / metabolism* Protein Isoforms / genetics Protein Isoforms / immunology Protein Isoforms / metabolism* RNA, Small Interfering / genetics RNA-Binding Proteins Signal Transduction / genetics Signal Transduction / immunology Virus Replication / genetics
IF 21.809
Human and Animal Cells MRC-5(RCB0211) known PDL(RCB0218)