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Sci. Signal., 7 January 2014
Vol. 7, Issue 307, p. ra3
[DOI: 10.1126/scisignal.2004577]

RESEARCH ARTICLES

Editor's Summary

Prolonging Antiviral Signaling
As part of the innate immune response to infection by RNA viruses, signaling by the cytosolic RNA sensor retinoic acid–inducible gene-I (RIG-I) stimulates the production of type I interferons (IFNs). RIG-I activity depends on its Lys63-linked polyubiquitylation by the ubiquitin E3 ligase TRIM25. As part of a negative feedback mechanism, the linear ubiquitin assembly complex (LUBAC) mediates the Lys48-linked polyubiquitylation and degradation of TRIM25, leading to inhibition of RIG-I signaling. Pauli et al. found that the deubiquitylase USP15 (ubiquitin-specific protease 15) counteracted the function of LUBAC by removing polyubiquitin from TRIM25, thus promoting its stabilization and enhancing the RIG-I–dependent antiviral response. Loss of USP15 resulted in decreased type I IFN production and enhanced viral replication in infected cells. Together, these data suggest that USP15 fine-tunes the antiviral response by sustaining the production of IFNs.

Citation: E.-K. Pauli, Y. K. Chan, M. E. Davis, S. Gableske, M. K. Wang, K. F. Feister, M. U. Gack, The Ubiquitin-Specific Protease USP15 Promotes RIG-I–Mediated Antiviral Signaling by Deubiquitylating TRIM25. Sci. Signal. 7, ra3 (2014).

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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M. U. Gack and A. M. VanHook (2014)
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