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We are analyzing https://www.nature.com/articles/s41598-017-12224-7.

Title:
Zyxin stabilizes RIG-I and MAVS interactions and promotes type I interferon response | Scientific Reports
Description:
RIG-I and MDA5 are cytoplasmic viral RNA sensors that belong to the RIG-I-like receptors (RLRs), which induce antiviral innate immune responses, including the production of type I interferon and other pro-inflammatory cytokines. After recognition of viral RNA, the N-terminal caspase activation and recruitment domains (CARDs) of RIG-I and MDA5 bind to a CARD in the MAVS adaptor molecule, resulting in MAVS oligomerization and downstream signaling. To reveal the molecular mechanism of MAVS-dependent signaling, we performed a yeast two-hybrid screening and identified zyxin as a protein that binds to MAVS. Zyxin co-immunoprecipitated with MAVS in human cells. A proximity ligation assay showed that zyxin and MAVS partly co-localized on mitochondria. Ectopic expression of zyxin augmented MAVS-mediated IFN-Ξ² promoter activation, and knockdown of zyxin (ZYX) attenuated the IFN-Ξ² promoter activation. Moreover, ZYX knockdown reduced the expression of type I IFN and an interferon-inducible gene after stimulation with polyI:C or influenza A virus RNA. Interestingly, physical interactions between RLRs and MAVS were abrogated by ZYX knockdown. These observations indicate that zyxin serves as a scaffold for the interactions between RLRs and MAVS.
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Keywords {πŸ”}

zyxin, cells, mavs, pubmed, article, rigi, fig, expression, google, scholar, zyx, cas, cell, signaling, transfected, activation, protein, antibody, ifnb, sirna, type, proteins, data, mda, rna, polyic, nature, performed, control, stimulation, zyxinha, antiviral, promoter, detected, central, viral, pla, innate, immune, flagmavs, card, ifn, region, plasmids, hela, rlrs, mavsmediated, knockdown, cterminal, antibodies,

Topics {βœ’οΈ}

nature portfolio privacy policy h-warts/lats1 tumor suppressor advertising regulate ifn-beta-inducing potential anti-Ξ²-actin mouse antibody medical research complement research tbk1/ikkepsilon-mediated irf activation nature immunology 5 social media pef-bos zyxin-c-ha nature communications 7 nature biotechnology 20 nature methods 3 promote rig-i-mediated type rig-i-mediated antiviral activity mediates k63-linked polyubiquitination facilitates rig-i-rna binding zyxin-s142a phospho-deficient mutation protein g-sepharose beads anti-phospho-zyxin monoclonal antibody double-stranded ribonucleic acids reprints anti-phospho-zyxin rabbit antibody ifn-Ξ² promoter activation pef-bos zyxin-n-ha nature 509 nature 446 nature 441 nature hrp-conjugated secondary antibody d-mem high glucose development rig-i-mavs complex required viral double-stranded rna d-mem low glucose c-terminal lim domains tbk-1-mediated irf-3 activation17 author information authors promote interferon-beta induction ifn-Ξ² protein levels thermo fisher scientific affect zyxin-mediated augmentation mfn2-mediated ubiquitin degradation tgf-beta signalling pathways n-terminal caspase activation reducing mavs-mediated signaling promoting mavs-mediated signaling phospho-deficient zyxin mutant

Schema {πŸ—ΊοΈ}

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         description:RIG-I and MDA5 are cytoplasmic viral RNA sensors that belong to the RIG-I-like receptors (RLRs), which induce antiviral innate immune responses, including the production of type I interferon and other pro-inflammatory cytokines. After recognition of viral RNA, the N-terminal caspase activation and recruitment domains (CARDs) of RIG-I and MDA5 bind to a CARD in the MAVS adaptor molecule, resulting in MAVS oligomerization and downstream signaling. To reveal the molecular mechanism of MAVS-dependent signaling, we performed a yeast two-hybrid screening and identified zyxin as a protein that binds to MAVS. Zyxin co-immunoprecipitated with MAVS in human cells. A proximity ligation assay showed that zyxin and MAVS partly co-localized on mitochondria. Ectopic expression of zyxin augmented MAVS-mediated IFN-β promoter activation, and knockdown of zyxin (ZYX) attenuated the IFN-β promoter activation. Moreover, ZYX knockdown reduced the expression of type I IFN and an interferon-inducible gene after stimulation with polyI:C or influenza A virus RNA. Interestingly, physical interactions between RLRs and MAVS were abrogated by ZYX knockdown. These observations indicate that zyxin serves as a scaffold for the interactions between RLRs and MAVS.
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      headline:Zyxin stabilizes RIG-I and MAVS interactions and promotes type I interferon response
      description:RIG-I and MDA5 are cytoplasmic viral RNA sensors that belong to the RIG-I-like receptors (RLRs), which induce antiviral innate immune responses, including the production of type I interferon and other pro-inflammatory cytokines. After recognition of viral RNA, the N-terminal caspase activation and recruitment domains (CARDs) of RIG-I and MDA5 bind to a CARD in the MAVS adaptor molecule, resulting in MAVS oligomerization and downstream signaling. To reveal the molecular mechanism of MAVS-dependent signaling, we performed a yeast two-hybrid screening and identified zyxin as a protein that binds to MAVS. Zyxin co-immunoprecipitated with MAVS in human cells. A proximity ligation assay showed that zyxin and MAVS partly co-localized on mitochondria. Ectopic expression of zyxin augmented MAVS-mediated IFN-β promoter activation, and knockdown of zyxin (ZYX) attenuated the IFN-β promoter activation. Moreover, ZYX knockdown reduced the expression of type I IFN and an interferon-inducible gene after stimulation with polyI:C or influenza A virus RNA. Interestingly, physical interactions between RLRs and MAVS were abrogated by ZYX knockdown. These observations indicate that zyxin serves as a scaffold for the interactions between RLRs and MAVS.
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      name:Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-Ku, Japan
      name:Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-Ku, Japan
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