Experimental immunology Potential role of RING finger protein 166 (RNF166), a member of an ubiquitin ligase subfamily, involved in regulation of T cell activation

Yang, Ping; Lu, Yilu; Jiang, Xuejun; Li, Min-Hui; Li, Chao; Chen, Huijuan; Zhang, Kun; Pan, Kehou; Tao, Dachang; Zhang, Sizhong; Ma, Yongxin

doi:10.5114/ceji.2013.34353

Cited by 5 publications

(3 citation statements)

References 17 publications

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“…Similarly, with its paralogue RNF125, LjRNF114, as a member of the RING-UIM family, contains an N-terminal RING finger domain, three zinc fingers (a C2HC domain and two C2H2-type zinc fingers) and a C-terminal UIM (39). In this study, we confirmed that LjRNF114 possessed ubiquitin E3 ligase activity, and UIM and RING domains were important for LjRNF114's ubiquitin ligase activity, which is consistent with previous studies (18,40). Lin et al (21) demonstrated that the E3 ligase activity of RNF114 is responsible for its regulating effect on immune response.…”

Section: Discussionsupporting

confidence: 91%

E3 Ubiquitin Ligase RNF114 Inhibits Innate Immune Response to Red-Spotted Grouper Nervous Necrosis Virus Infection in Sea Perch by Targeting MAVS and TRAF3 to Mediate Their Degradation

Xiang

Zhang

Jia

et al. 2021

The Journal of Immunology

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RIG-I–like receptor (RLR)–mediated antiviral signaling is critical to trigger the immune response to virus infection; however, the antiviral responses are also tightly regulated to avoid uncontrolled production of type I IFN by various mechanisms, including ubiquitination. In this study, an E3 ubiquitin ligase ring finger protein 114 (RNF114) from sea perch (Lateolabrax japonicus) (LjRNF114) was identified as a suppressor of RLR signaling pathways during red-spotted grouper nervous necrosis virus (RGNNV) infection. RGNNV infection promoted the expression of LjRNF114. Overexpression of LjRNF114 enhanced RGNNV replication, whereas knockdown of LjRNF114 led to opposite effects. Type I IFN production induced by RGNNV was suppressed by LjRNF114, which is dependent on its ubiquitin ligase activity. Moreover, LjRNF114 inhibited IFN promoter activation induced by key signaling molecules in RLR signaling pathways. We observed the interactions between LjRNF114 and both sea perch mitochondrial antiviral signaling protein (MAVS) and TNFR-associated factor 3 (TRAF3). Domain mapping experiments indicated that the RING and ubiquitin interacting motif domains of LjRNF114 were required for its interaction with TRAF3 and MAVS. We found that LjRNF114 targeted MAVS and TRAF3 for K27- and K48-linked ubiquitination and degradation, resulting in the inhibition of IFN production. Taken together, our study reveals, to our knowledge, a novel mechanism that LjRNF114 targets and promotes K27- and K48-linked ubiquitination of MAVS and TRAF3 to negatively regulate the RLR signaling pathways, promoting viral infection.

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Section: Discussionsupporting

confidence: 91%

E3 Ubiquitin Ligase RNF114 Inhibits Innate Immune Response to Red-Spotted Grouper Nervous Necrosis Virus Infection in Sea Perch by Targeting MAVS and TRAF3 to Mediate Their Degradation

Xiang

Zhang

Jia

et al. 2021

The Journal of Immunology

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“…Several studies have identified that the RING-UIM family members, including RNF114, RNF125, and RNF166, positively regulate T cell activation. 33,[314][315][316] These three members act as the positive regulators of TCR signaling-mediated T cell activation, using surface CD69 expression as a surrogate marker for cell activation. Silencing the RNF125 dramatically suppresses T cell activation in response to TCR cross-linking, and overexpression of RNF114 and RNF166 significantly upregulates the CD69 expression.…”

Section: Adaptive Immune Responsesmentioning

confidence: 99%

The RING finger protein family in health and disease

Cai

Tang

Zhai³

et al. 2022

Sig Transduct Target Ther

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Ubiquitination is a highly conserved and fundamental posttranslational modification (PTM) in all eukaryotes regulating thousands of proteins. The RING (really interesting new gene) finger (RNF) protein, containing the RING domain, exerts E3 ubiquitin ligase that mediates the covalent attachment of ubiquitin (Ub) to target proteins. Multiple reviews have summarized the critical roles of the tripartite-motif (TRIM) protein family, a subgroup of RNF proteins, in various diseases, including cancer, inflammatory, infectious, and neuropsychiatric disorders. Except for TRIMs, since numerous studies over the past decades have delineated that other RNF proteins also exert widespread involvement in several diseases, their importance should not be underestimated. This review summarizes the potential contribution of dysregulated RNF proteins, except for TRIMs, to the pathogenesis of some diseases, including cancer, autoimmune diseases, and neurodegenerative disorder. Since viral infection is broadly involved in the induction and development of those diseases, this manuscript also highlights the regulatory roles of RNF proteins, excluding TRIMs, in the antiviral immune responses. In addition, we further discuss the potential intervention strategies targeting other RNF proteins for the prevention and therapeutics of those human diseases.

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“…Recently, other members including RNF166 and RNF114 were reported subsequently. The overexpression of RNF166 in primary T cells and Jurkat T cells induces over 2-fold increase of CD69, a T-cell activation marker, suggesting that RNF166 is also a positive regulator of T cell activation ( 89 ). RNF114 is a novel positive regulator of T cell activation, in which the C 2 H 2 domain is involved in this process ( 90 ).…”

Section: Host Ring E3s As Immune Regulatorsmentioning

confidence: 99%

RING-Domain E3 Ligase-Mediated Host–Virus Interactions: Orchestrating Immune Responses by the Host and Antagonizing Immune Defense by Viruses

Zhang

Munir

et al. 2018

Front. Immunol.

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The RING-domain E3 ligases (RING E3s), a group of E3 ligases containing one or two RING finger domains, are involved in various cellular processes such as cell proliferation, immune regulation, apoptosis, among others. In the host, a substantial number of the RING E3s have been implicated to inhibit viral replication through regulating immune responses, including activation and inhibition of retinoic acid-inducible gene I-like receptors, toll-like receptors, and DNA receptor signaling pathways, modulation of cell-surface expression of major histocompatibility complex, and co-stimulatory molecules. During the course of evolution and adaptation, viruses encode RING E3s to antagonize host immune defense, such as the infected cell protein 0 of herpes simplex virus type 1, the non-structural protein 1 of rotavirus, and the K3 and K5 of Kaposi’s sarcoma-associated herpesvirus. In addition, recent studies suggest that viruses can hijack the host RING E3s to facilitate viral replication. Based on emerging and interesting discoveries, the RING E3s present novel links among the host and viruses. Herein, we focus on the latest research progresses in the RING E3s-mediated host–virus interactions and discuss the outlooks of the RING E3s for future research.

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Experimental immunology Potential role of RING finger protein 166 (RNF166), a member of an ubiquitin ligase subfamily, involved in regulation of T cell activation

Cited by 5 publications

References 17 publications

E3 Ubiquitin Ligase RNF114 Inhibits Innate Immune Response to Red-Spotted Grouper Nervous Necrosis Virus Infection in Sea Perch by Targeting MAVS and TRAF3 to Mediate Their Degradation

E3 Ubiquitin Ligase RNF114 Inhibits Innate Immune Response to Red-Spotted Grouper Nervous Necrosis Virus Infection in Sea Perch by Targeting MAVS and TRAF3 to Mediate Their Degradation

The RING finger protein family in health and disease

RING-Domain E3 Ligase-Mediated Host–Virus Interactions: Orchestrating Immune Responses by the Host and Antagonizing Immune Defense by Viruses

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