2024-03-29T14:46:07Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/467622022-11-17T02:08:08Zhdl_2115_20058hdl_2115_149ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I during antiviral responsesHayakawa, SumioShiratori, SouichiYamato, HiroakiKameyama, TakeshiKitatsuji, ChihiroKashigi, FumiGoto, ShowheyKameoka, ShoichiroFujikura, DaisukeYamada, TaishoMizutani, TatsuakiKazumata, MikaSato, MaikoTanaka, JunjiAsaka, MasahiroOhba, YusukeMiyazaki, TadaakiImamura, MasahiroTakaoka, Akinori491The poly(ADP-ribose) polymerases (PARPs) participate in various processes. Here, we report that the PARP-13/ZAP shorter isoform (hereafter called ZAPS), rather than the full length protein, is selectively induced by 3pRNA, and functions as a potent stimulator of retinoic acid-inducible gene-I (RIG-I)-mediated interferon (IFN) responses in human cells. ZAPS associates with RIG-I to promote the oligomerization and ATPase activity of RIG-I, leading to robust activation of IRF3 and NF-κB pathways. Disruption of the PARP-13/ZAP gene, ZC3HAV1, severely abrogated the induction of IFN-α, IFN-β and other cytokines upon viral infection. These results indicate that ZAPS is a key regulator of RIG-I signaling during the innate antiviral immune response, suggesting its possible use as a therapeutic target for viral control.Nature Publishing GroupJournal Articleapplication/pdfapplication/pdfhttp://hdl.handle.net/2115/46762https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/46762/2/NI12-1_37-44.pdfhttps://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/46762/1/SupplementaryTextAndFigures.pdf1529-2908Nature Immunology12137442011-01enginfo:pmid/21102435info:doi/10.1038/ni.1963author