E3 ubiquitin ligase CHIP facilitates Toll-like receptor signaling by recruiting and polyubiquitinating Src and atypical PKCζ

Yang, Mingjin; Wang, Chen; Zhu, Xuhui; Tang, Songqing; Shi, Liyun; Cao, Xuetao; Chen, Taoyong

doi:10.1084/jem.20102667

Cited by 87 publications

(78 citation statements)

References 49 publications

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“…HA-CHIP-expressing plasmid was a gift from Mingjin Yang (Institute of Immunology, Second Military Medical University) 33 . Flag-Stk38 construct was a gift from Xiaojian Wang (Institute of Immunology, Zhejiang University).…”

Section: Methodsmentioning

confidence: 99%

Stk38 protein kinase preferentially inhibits TLR9-activated inflammatory responses by promoting MEKK2 ubiquitination in macrophages

Wen

Cheng

et al. 2015

Nat Commun

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Section: Methodsmentioning

confidence: 99%

Stk38 protein kinase preferentially inhibits TLR9-activated inflammatory responses by promoting MEKK2 ubiquitination in macrophages

Wen

Cheng

et al. 2015

Nat Commun

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“…), protein kinases (calmodulin-dependent protein kinase II, Btk, MEKK3, [12][13][14] etc. ), ubiquitin-related proteins (A20, Nrdp1, CHIP, [15][16][17] etc. ), Nodlike family proteins (NLRX1, NLRC5, 18,19 etc.…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs in the regulation of TLR and RIG-I pathways

2012

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The innate immune system recognizes invading pathogens through germline-encoded pattern recognition receptors (PRRs), which elicit innate antimicrobial and inflammatory responses and initiate adaptive immunity to control or eliminate infection. Toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I) are the key innate immune PRRs and are tightly regulated by elaborate mechanisms to ensure a beneficial outcome in response to foreign invaders. Although much of the focus in the literature has been on the study of protein regulators of inflammation, microRNAs (miRNAs) have emerged as important controllers of certain features of the inflammatory process. Several miRNAs are induced by TLR and RIG-I activation in myeloid cells and act as feedback regulators of TLR and RIG-I signaling. In this review, we comprehensively discuss the recent understanding of how miRNA networks respond to TLR and RIG-I signaling and their role in the initiation and termination of inflammatory responses. Increasing evidence also indicates that both virus-encoded miRNAs and cellular miRNAs have important functions in viral replication and host anti-viral immunity.

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“…GST and GST-RIG-I WT and GST-RIG-I CARDs were expressed in BL21DE Escherichia coli cells and purified by using previously described methods (36). The GST pull-down assay was performed as described previously (37).…”

Section: Methodsmentioning

confidence: 99%

RNF122 suppresses antiviral type I interferon production by targeting RIG-I CARDs to mediate RIG-I degradation

Wang

Jiang

Liu

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The activation of retinoic acid-inducible gene 1 (RIG-I), a cytoplasmic innate sensor for viral RNA, is tightly regulated to maintain immune homeostasis properly and prevent excessive inflammatory reactions other than initiation of antiviral innate response to eliminate RNA virus effectively. Posttranslational modifications, particularly ubiquitination, are crucial for regulation of RIG-I activity. Increasing evidence suggests that E3 ligases play important roles in various cellular processes, including cell proliferation and antiviral innate signaling. Here we identify that E3 ubiquitin ligase RING finger protein 122 (RNF122) directly interacts with mouse RIG-I through MS screening of RIG-Iinteracting proteins in RNA virus-infected cells. The transmembrane domain of RNF122 associates with the caspase activation and recruitment domains (CARDs) of RIG-I; this interaction effectively triggers RING finger domain of RNF122 to deliver the Lys-48-linked ubiquitin to the Lys115 and Lys146 residues of RIG-I CARDs and promotes RIG-I degradation, resulting in a marked inhibition of RIG-I downstream signaling. RNF122 is widely expressed in various immune cells, with preferential expression in macrophages. Deficiency of RNF122 selectively increases RIG-I-triggered production of type I IFNs and proinflammatory cytokines in macrophages. RNF122-deficient mice exhibit more resistance against lethal RNA virus infection, with increased production of type I IFNs. Thus, we demonstrate that RNF122 acts as a selective negative regulator of RIG-I-triggered antiviral innate response by targeting CARDs of RIG-I and mediating proteasomal degradation of RIG-I. Our study outlines a way for E3 ligase to regulate innate sensor RIG-I for the control of antiviral innate immunity.RIG-I | E3 ligase | RNF122 | innate immunity | type I interferon

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E3 ubiquitin ligase CHIP facilitates Toll-like receptor signaling by recruiting and polyubiquitinating Src and atypical PKCζ

Abstract: In mouse macrophages and dendritic cells, the CHIP E3 ubiquitin ligase is needed for transduction of signals initiated by TLR4 and TLR9 stimulation.

Cited by 87 publications

References 49 publications

Stk38 protein kinase preferentially inhibits TLR9-activated inflammatory responses by promoting MEKK2 ubiquitination in macrophages

Stk38 protein kinase preferentially inhibits TLR9-activated inflammatory responses by promoting MEKK2 ubiquitination in macrophages

MicroRNAs in the regulation of TLR and RIG-I pathways

RNF122 suppresses antiviral type I interferon production by targeting RIG-I CARDs to mediate RIG-I degradation

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