REUL is a Novel E3 Ubiquitin Ligase and Stimulator of Retinoic-acid-inducible Gene-I

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2009 Jun 2

PMID 19484123

Citations 80

Authors

Dong Gao

Yong-Kang Yang

Rui-Peng Wang

Xiang Zhou

Fei-Ci Diao

Min-Dian Li

Zhong-He Zhai

Zheng-Fan Jiang

Dan-Ying Chen

Affiliations

Soon will be listed here.

Abstract

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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