| Title | ARF-like Protein 16 (ARL16) Inhibits RIG-I by Binding with Its C-terminal Domain in a GTP-dependent Manner |
| Authors | Yang, Yong-Kang Qu, Hong Gao, Dong Di, Wei Chen, Hai-Wei Guo, Xin Zhai, Zhong-He Chen, Dan-Ying |
| Affiliation | Peking Univ, Coll Life Sci, Key Lab Cell Proliferat & Differentiat, Minist Educ, Beijing 100871, Peoples R China. China Agr Univ, Key Lab Zoonosis, Minist Agr, Beijing 100083, Peoples R China. |
| Keywords | NEGATIVE FEEDBACK-REGULATION ANTIVIRAL INNATE IMMUNITY E3 UBIQUITIN LIGASE NF-KAPPA-B ADAPTER PROTEIN SWISS-MODEL ENDOPLASMIC-RETICULUM GOLGI-APPARATUS RNA HELICASE SAR PROTEINS |
| Issue Date | 2011 |
| Publisher | journal of biological chemistry |
| Citation | JOURNAL OF BIOLOGICAL CHEMISTRY.2011,286,(12),10568-10580. |
| Abstract | Retinoic acid-inducible gene I (RIG-I) recognizes RNA virus-derived nucleic acids, which leads to the production of type I interferon (IFN) in most cell types. Tight regulation of RIG-I activity is important to prevent ultra-immune responses. In this study, we identified an ARF-like (ARL) family member, ARL16, as a protein that interacts with RIG-I. Overexpression of ARL16, but not its homologous proteins ARL1 and ARF1, inhibited RIG-I-mediated downstream signaling and antiviral activity. Knockdown of endogenous ARL16 by RNAi potentiated Sendai virus-induced IFN-beta expression and vesicular stomatitis virus replication. ARL16 interacted with the C-terminal domain (CTD) of RIG-I to suppress the association between RIG-I and RNA. ARL16 (T37N) and ARL16 Delta 45-54, which were restricted to the GTP-disassociated form, did not interact with RIG-I and also lost the inhibitory function. Furthermore, we suggest that endogenous ARL16 changes to GTP binding status upon viral infection and binds with the RIG-I CTD to negatively control its signaling activity. These findings suggested a novel innate immune function for an ARL family member, and a GTP-dependent model in which RIG-I is regulated. |
| URI | http://hdl.handle.net/20.500.11897/319967 |
| ISSN | 0021-9258 |
| DOI | 10.1074/jbc.M110.206896 |
| Indexed | SCI(E) EI PubMed |
| Appears in Collections: | 生命科学学院 细胞增殖分化调控机理研究教育部重点实验室 |
