reul is a novel e3 ubiquitin ligase and stimulator of retinoic-acid-inducible gene-i勒尔是一种新型的e3泛素连接酶和刺激器retinoic-acid-inducible基因.pdfVIP

REUL Is a Novel E3 Ubiquitin Ligase and Stimulator of Retinoic-Acid-Inducible Gene-I 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* Key Laboratory of Cell Proliferation and Differentiation (Ministry of Education), College of Life Sciences, Peking University, Beijing, China 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-kB, 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-b promoter. Knockdown of endogenous REUL by RNAi inhibited SV-triggered IFN-b 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-b promoter. These findings suggest that REUL is an E3 ubiquitin ligase of RIG-I and specifically stimulates RIG-I-mediated innate antiviral activity. Citation: Gao D, Yang Y-K, Wang R-P, Zhou X, Diao F-C, et al. (2009) REUL Is a Novel E3 Ubiquitin Ligase and Stimulator of Retinoic-Acid-Inducible Gene-I. PLoS ONE 4(6): e5760. doi:10.1371/journal.pone.0005760 ´ Editor: Jerome Nigou, Institut de Pharmacologie et de Biologie