SUMOylation of RIG-I positively regulates the type I interferon signaling

Center for Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Protein & Cell (Impact Factor: 3.25). 03/2010; 1(3):275-83. DOI: 10.1007/s13238-010-0030-1
Source: PubMed


Retinoic acid-inducible gene-I (RIG-I) functions as an intracellular pattern recognition receptor (PRR) that recognizes the 5'-triphosphate moiety of single-stranded RNA viruses to initiate the innate immune response. Previous studies have shown that Lys63-linked ubiquitylation is required for RIG-I activation and the downstream anti-viral type I interferon (IFN-I) induction. Herein we reported that, RIG-I was also modified by small ubiquitin-like modifier-1 (SUMO-1). Functional analysis showed that RIG-I SUMOylation enhanced IFN-I production through increased ubiquitylation and the interaction with its downstream adaptor molecule Cardif. Our results therefore suggested that SUMOylation might serve as an additional regulatory tier for RIG-I activation and IFN-I signaling.

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    • "The innate response is triggered by recognition of pathogen-specific molecules by the Toll-like receptor (TLR) system which then initiates a signaling cascade that activates IRFs 3, 5, and 7 via phosphorylation; the activated IRFs turn on interferon transcription. Two of the TLRs, RIG-1 [47] and MDA5 [48], and an adaptor protein in the TLR signaling pathway known as Pellino-1 [49] have recently been shown to be sumoylated proteins. Sumoylation of RIG-1 enhanced its association with Cardif and led to increased expression of interferon β. "
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    ABSTRACT: Many viral proteins have been shown to be sumoylated with corresponding regulatory effects on their protein function, indicating that this host cell modification process is widely exploited by viral pathogens to control viral activity. In addition to using sumoylation to regulate their own proteins, several viral pathogens have been shown to modulate overall host sumoylation levels. Given the large number of cellular targets for SUMO addition and the breadth of critical cellular processes that are regulated via sumoylation, viral modulation of overall sumoylation presumably alters the cellular environment to ensure that it is favorable for viral reproduction and/or persistence. Like some viruses, certain bacterial plant pathogens also target the sumoylation system, usually decreasing sumoylation to disrupt host anti-pathogen responses. The recent demonstration that Listeria monocytogenes also disrupts host sumoylation, and that this is required for efficient infection, extends the plant pathogen observations to a human pathogen and suggests that pathogen modulation of host sumoylation may be more widespread than previously appreciated. This review will focus on recent aspects of how pathogens modulate the host sumoylation system and how this benefits the pathogen.
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    • "Further study indicates that S8 and T170 of RIG-I are two other phosphorylation sites to keep RIG-I latent (Gack et al., 2010; NistalVillán et al., 2010). In addition to ubiquitylation and phosphorylation, recent study reports that RIG-I is also modified by small ubiquitin-like modifier-1 (SUMO-1), which enhances type I IFN production (Mi et al., 2010). "
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    ABSTRACT: Retinoic acid inducible gene-I (RIG-I) is a caspase recruitment domain (CARD) containing protein that acts as an intracellular RNA receptor and senses virus infection. After binding to double stranded RNA (dsRNA) or 5'-triphosphate single stranded RNA (ssRNA), RIG-I transforms into an open conformation, translocates onto mitochondria, and interacts with the downstream adaptor mitochondrial antiviral signaling (MAVS) to induce the production of type I interferon and inflammatory factors via IRF3/7 and NF-κB pathways, respectively. Recently, accumulating evidence suggests that RIG-I could function in non-viral systems and participate in a series of biological events, such as inflammation and inflammation related diseases, cell proliferation, apoptosis and even senescence. Here we review recent advances in antiviral study of RIG-I as well as the functions of RIG-I in other fields.
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