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ARF-like Protein 16 (ARL 16) Inhibits RIG-I by Binding with Its C-terminal Domain in a GTP-dependent Manner.
- Source :
-
Journal of Biological Chemistry . 3/25/2011, Vol. 286 Issue 12, p10568-10580. 13p. - Publication Year :
- 2011
-
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 ARE-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-β 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 ARL16Δ5-54, 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 286
- Issue :
- 12
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 62992672
- Full Text :
- https://doi.org/10.1074/jbc.M110.206896