MAVS ubiquitination by the E3 ligase TRIM25 and degradation by the proteasome is involved in type I Interferon production after activation of the antiviral RIG-I-Like receptors. - Archive ouverte HAL Access content directly
Journal Articles BMC Biology Year : 2012

MAVS ubiquitination by the E3 ligase TRIM25 and degradation by the proteasome is involved in type I Interferon production after activation of the antiviral RIG-I-Like receptors.

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Abstract

ABSTRACT: BACKGROUND: During a viral infection, the intracellular RIG-I-like receptors (RLRs) sense viral RNA and signal through the mitochondrial antiviral signaling adaptor MAVS (also known as IPS-1, Cardif and VISA) whose activation triggers a rapid production of type I interferons (IFN) and of pro-inflammatory cytokines through the transcription factors IRF3/IRF7 and NF-kappaB, respectively. While MAVS is essential for this signaling and known to operate through the scaffold protein NEMO and the protein kinase TBK1 that phosphorylates IRF3, its mechanism of action and regulation remain unclear. RESULTS: We report here that RLR activation triggers MAVS ubiquitination on lysine 7 and 10 by the E3 ubiquitin ligase TRIM25 and marks it for proteasomal degradation concomitantly with downstream signaling. Inhibition of this MAVS degradation with a proteasome inhibitor does not affect NF-kappaB signaling but it hampers IRF3 activation, and NEMO and TBK1, two essential mediators in type I IFN production, are retained at the mitochondria. CONCLUSIONS: These results suggest that MAVS functions as a recruitment platform that assembles a signaling complex involving NEMO and TBK1, and that the proteasome-mediated MAVS degradation is required to release the signaling complex into the cytosol, allowing IRF3 phosphorylation by TBK1.
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Dates and versions

inserm-00706690 , version 1 (11-06-2012)

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Céline Castanier, Naima Zemirli, Alain Portier, Dominique Garcin, Nicolas Bidère, et al.. MAVS ubiquitination by the E3 ligase TRIM25 and degradation by the proteasome is involved in type I Interferon production after activation of the antiviral RIG-I-Like receptors.. BMC Biology, 2012, 10 (1), pp.44. ⟨10.1186/1741-7007-10-44⟩. ⟨inserm-00706690⟩
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