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- W2168575145 abstract "Abstract Members of the protein inhibitor of activated STAT (PIAS) family are key regulators of various human and mammalian signaling pathways, but data on their occurrence and functions in ancient vertebrates are limited. This study characterizes for the first time to our knowledge a PIAS4 homologue (PIAS4a) from zebrafish. Structurally, this zebrafish PIAS4a (zfPIAS4a) shares a number of conserved functional domains with mammalian PIAS4 proteins, including the scaffold attachment factor A/B/acinus/PIAS box, PINIT, and RING-finger–like zinc-binding domains and a highly acidic domain in the C-terminal region. Subcellular localization analysis shows that zfPIAS4a is a nuclear-localized protein and that the C terminus of the molecule harbors strict nuclear localization signals. Functionally, zfPIAS4a expression can be dramatically induced by the stimulation of polyinosinic-polycytidylic acid and zebrafish IFNϕ1. It acts as a critical negative regulator of the TIR domain-containing adapter inducing IFN-β, mitochondrial antiviral signaling (MAVS), and IFN signaling pathways, and it is the first PIAS protein that plays a role in the MAVS-mediated pathway to be identified. The structure and functionality of PIAS4 seem highly conserved from zebrafish to mammals, making zebrafish an attractive model for screens designed to uncover genes involved in IFN- and inflammatory cytokine-induced signaling pathways. This study provides preliminary evidence that the PIAS regulatory mechanism already existed in fish during vertebrate evolution. It presents valuable clues for improving the understanding of not only the negative regulation of cytokine signaling in fish but also the evolutionary history of the PIAS family from fish to mammals as a whole." @default.
- W2168575145 created "2016-06-24" @default.
- W2168575145 creator A5012365466 @default.
- W2168575145 creator A5013447710 @default.
- W2168575145 creator A5054634752 @default.
- W2168575145 creator A5082747056 @default.
- W2168575145 date "2012-03-15" @default.
- W2168575145 modified "2023-10-03" @default.
- W2168575145 title "Characterization of a PIAS4 Homologue from Zebrafish: Insights into Its Conserved Negative Regulatory Mechanism in the TRIF, MAVS, and IFN Signaling Pathways during Vertebrate Evolution" @default.
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- W2168575145 doi "https://doi.org/10.4049/jimmunol.1100959" @default.
- W2168575145 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22345667" @default.
- W2168575145 hasPublicationYear "2012" @default.
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