REUL is a novel E3 ubiquitin ligase and stimulator of retinoic-acid-inducible gene-I.

Authors:
Dong Gao
Dong Gao
Memorial Sloan Kettering Cancer Center
Rockville Centre | United States
Xiang Zhou
Xiang Zhou
College of Chemistry and Molecular Sciences
Wuhan Shi | China
Dr. Min-Dian Li, PhD
Dr. Min-Dian Li, PhD
Harvard TH Chan School of Public Health
Postdoctoral Fellow
Cellular and Molecular Physiology
Boston, MA | United States

PLoS One 2009 Jun 1;4(6):e5760. Epub 2009 Jun 1.

Key Laboratory of Cell Proliferation and Differentiation (Ministry of Education), College of Life Sciences, Peking University, Beijing, China.

RIG-I and MDA5 are cytoplasmic sensors that recognize different species of viral RNAs, leads to activation of the transcription factors IRF3 and NF-kappaB, which collaborate to induce type I interferons. In this study, we identified REUL, a RING-finger protein, as a specific RIG-I-interacting protein. REUL was associated with RIG-I, but not MDA5, through its PRY and SPRY domains. Overexpression of REUL potently potentiated RIG-I-, but not MDA5-mediated downstream signalling and antiviral activity. In contrast, the RING domain deletion mutant of REUL suppressed Sendai virus (SV)-induced, but not cytoplasmic polyI:C-induced activation of IFN-beta promoter. Knockdown of endogenous REUL by RNAi inhibited SV-triggered IFN-beta expression, and also increased VSV replication. Full-length RIG-I, but not the CARD domain deletion mutant of RIG-I, underwent ubiquitination induced by REUL. The Lys 154, 164, and 172 residues of the RIG-I CARD domain were critical for efficient REUL-mediated ubiquitination, as well as the ability of RIG-I to induce activation of IFN-beta promoter. These findings suggest that REUL is an E3 ubiquitin ligase of RIG-I and specifically stimulates RIG-I-mediated innate antiviral activity.

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0005760PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2684588PMC

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June 2009
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