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- Title
ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I during antiviral responses.
- Authors
Hayakawa, Sumio; Shiratori, Souichi; Yamato, Hiroaki; Kameyama, Takeshi; Kitatsuji, Chihiro; Kashigi, Fumi; Goto, Showhey; Kameoka, Shoichiro; Fujikura, Daisuke; Yamada, Taisho; Mizutani, Tatsuaki; Kazumata, Mika; Sato, Maiko; Tanaka, Junji; Asaka, Masahiro; Ohba, Yusuke; Miyazaki, Tadaaki; Imamura, Masahiro; Takaoka, Akinori
- 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.
- Subjects
DRUG synergism; ISOMERASES; NF-kappa B; ANTIVIRAL agents; TRANSCRIPTION factors; VIRUS diseases; IMMUNE response; ENZYME activation; INTERFERONS
- Publication
Nature Immunology, 2011, Vol 12, Issue 1, p37
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.1963