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Ubiquitin-regulated recruitment of IkappaB kinase epsilon to the MAVS interferon signaling adapter.

Abstract : Induction of the antiviral interferon response is initiated upon recognition of viral RNA structures by the RIG-I or Mda-5 DEX(D/H) helicases. A complex signaling cascade then converges at the mitochondrial adapter MAVS, culminating in the activation of the IRF and NF-kappaB transcription factors and the induction of interferon gene expression. We have previously shown that MAVS recruits IkappaB kinase epsilon (IKKepsilon) but not TBK-1 to the mitochondria following viral infection. Here we map the interaction of MAVS and IKKepsilon to the C-terminal region of MAVS and demonstrate that this interaction is ubiquitin dependent. MAVS is ubiquitinated following Sendai virus infection, and K63-linked ubiquitination of lysine 500 (K500) of MAVS mediates recruitment of IKKepsilon to the mitochondria. Real-time PCR analysis reveals that a K500R mutant of MAVS increases the mRNA level of several interferon-stimulated genes and correlates with increased NF-kappaB activation. Thus, recruitment of IKKepsilon to the mitochondria upon MAVS K500 ubiquitination plays a modulatory role in the cascade leading to NF-kappaB activation and expression of inflammatory and antiviral genes. These results provide further support for the differential role of IKKepsilon and TBK-1 in the RIG-I/Mda5 pathway.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-00460541
Contributor : Mireille Gau <>
Submitted on : Monday, March 1, 2010 - 3:31:57 PM
Last modification on : Monday, July 20, 2020 - 12:34:51 PM

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Suzanne Paz, Myriam Vilasco, Meztli Arguello, Qiang Sun, Judith Lacoste, et al.. Ubiquitin-regulated recruitment of IkappaB kinase epsilon to the MAVS interferon signaling adapter.. Molecular and Cellular Biology, American Society for Microbiology, 2009, 29 (12), pp.3401-12. ⟨10.1128/MCB.00880-08⟩. ⟨pasteur-00460541⟩

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