Induction of USP25 by viral infection promotes innate antiviral responses by mediating the stabilization of TRAF3 and TRAF6

Lin, Dandan; Zhang, Man; Zhang, Meng-Xin; Ren, Yujie; Jin, Jie; Zhao, Quanyi; Pan, Zishu; Wu, Min; Shu, Hong‐Bing; Dong, Chen; Zhong, Bo

doi:10.1073/pnas.1509968112

Cited by 103 publications

(102 citation statements)

References 39 publications

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“…We have previously observed that LPS or viral infection substantially up-regulates the expression of Usp25 gene (31,32). In this study, we found that virus-or LPS-induced expression of Usp25 was significantly abolished in cells lacking IRF7 or IFNAR1.…”

Section: Viral Infection or Lipopolysaccharide (Lps) Treatment Inducesmentioning

confidence: 46%

“…In our previous studies, we have observed that the expression of Usp25 is up-regulated by LPS treatment or viral infection in various types of cells (31,32). Interestingly, treatment with actinomycin D, a compound that inhibits transcription, almost abolished the up-regulation of Usp25 and the increase of USP25 protein by LPS or SeV or HSV-1 infection in BMDCs (Fig.…”

Section: Irf7 Plays An Essential Role Of Lps-or Virus-induced Expressmentioning

confidence: 70%

“…Data were normalized to the expression of ␤-actin. Real time quantitative PCR primers were described previously (31) Virus-mediated Gene Transfer-For lentivirus-mediated gene transfer, phage-6tag-IRF3, phage-6tag-IRF7, phage-6tag-rTBK1, phage-6tag-rIKK⑀, or the empty vector was cotransfected with the packaging vectors pSPAX2 and pMD2G into HEK293T cells. Eight hours after transfection, the medium was changed with fresh full medium (10% FBS, 1% streptomycinpenicillin, and 10 M ␤-mercaptoethanol).…”

Section: Mice-ifnar1mentioning

confidence: 99%

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The Type I Interferon-IRF7 Axis Mediates Transcriptional Expression of Usp25 Gene

Ren

Zhao

Lin

et al. 2016

Journal of Biological Chemistry

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Viral infection or lipopolysaccharide (LPS) treatment inducesexpression of a large array of genes, the products of which play a critical role in host antipathogen immunity and inflammation. We have previously reported that the expression of ubiquitinspecific protease 25 (USP25) is significantly up-regulated after viral infection or LPS treatment, and this is essential for innate immune signaling. However, the mechanism behind this phenomenon is unclear. In this study, we found that viral infectioninduced up-regulation of Usp25 is diminished in cells lacking interferon regulatory factor 7 (IRF7) or interferon ␣ receptor 1 (IFNAR1) but not p65. Sendai virus-or type I interferon-induced up-regulation of Usp25 requires de novo protein synthesis of IRF7. Furthermore, IRF7 directly binds to the two conserved IRF binding sites on the USP25 promoter to drive transcription of Usp25, and mutation of these two sites abolished Sendai virus-induced IRF7-mediated activation of the USP25 promoter. Our study has uncovered a previously unknown mechanism by which viral infection or LPS induces up-regulation of USP25.Host pattern recognition receptors recognize pathogen-associated molecular patterns and initiate a series of signaling cascades that lead to activation of transcription factors including NF-B and interferon regulatory factor 3 (IRF3) 2 (1-3). It has been well documented that activation of NF-B (p65/p50 heterodimer) is dependent on inhibitors of B kinase (IKK) complex (IKK␣/␤/␥)-mediated phosphorylation and degradation of IB␣, whereas activation of IRF3 requires phosphorylation by TBK1 or IKK⑀ (4 -9). The activated NF-B and IRF3 enter into nucleus, bind to the conserved B or IRF binding sites of promoters, and recruit co-activators to activate the transcription of target genes.Viral nucleic acid and lipopolysaccharide (LPS) of Gramnegative bacteria are two common pathogen-associated molecular patterns that trigger signaling cascades to activate NF-B and IRF3 and induce the production of type I interferons (IFNs) (3, 10). Type I IFNs further induce the expression of hundreds of downstream genes in an autocrine or paracrine manner, and the products of these genes including interferon-induced GTPbinding protein (Mx), 2Ј-5Ј-oligoadenylate synthase (OAS), double-stranded RNA-activated protein kinase (PKR), ISG56, and ISG15 orchestrate inhibition of pathogen replication and spread and promote apoptosis and clearance of the infected cells (11). In addition to the direct effect on innate immune cells for antipathogen responses, type I IFNs also regulate adaptive immunity including T cell activation and differentiation and antitumor immunity (12, 13).The type I IFN family is composed of 13 functional IFNA genes in humans (14 in mice), a single IFNB gene, and others. The IFN␣ family shares 80% sequence homology among them, whereas the homology between various IFN␣ and IFN␤ is 30% (14, 15). However, all the type I IFNs bind to the same receptors, IFNAR1 and IFNAR2, with affinities varying from picomolar to micromolar orders to re...

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Section: Viral Infection or Lipopolysaccharide (Lps) Treatment Inducesmentioning

confidence: 46%

Section: Irf7 Plays An Essential Role Of Lps-or Virus-induced Expressmentioning

confidence: 70%

Section: Mice-ifnar1mentioning

confidence: 99%

See 1 more Smart Citation

The Type I Interferon-IRF7 Axis Mediates Transcriptional Expression of Usp25 Gene

Ren

Zhao

Lin

et al. 2016

Journal of Biological Chemistry

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“…Heterooligomerization may also account for the remnant degradation levels of the inactive Trp40Ala variant. A second possibility is that the phosphorylated variant is recognized by an additional stabilizing factor such as a ubiquitin-specific protease that contributes to its stabilization, as shown for TRIM25 and TRAF6 (Pauli et al, 2014;Lin et al, 2015a).…”

Section: Autoubiquitination a Mechanism Of Self-regulation?mentioning

confidence: 99%

Changes in PUB22 Ubiquitination Modes Triggered by MITOGEN-ACTIVATED PROTEIN KINASE3 Dampen the Immune Response

et al. 2017

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Crosstalk between posttranslational modifications, such as ubiquitination and phosphorylation, play key roles in controlling the duration and intensity of signaling events to ensure cellular homeostasis. However, the molecular mechanisms underlying the regulation of negative feedback loops remain poorly understood. Here, we uncover a pathway in Arabidopsis thaliana by which a negative feedback loop involving the E3 ubiquitin ligase PUB22 that dampens the immune response is triggered by MITOGEN-ACTIVATED PROTEIN KINASE3 (MPK3), best known for its function in the activation of signaling. PUB22's stability is controlled by MPK3-mediated phosphorylation of residues localized in and adjacent to the E2 docking domain. We show that phosphorylation is critical for stabilization by inhibiting PUB22 oligomerization and, thus, autoubiquitination. The activity switch allows PUB22 to dampen the immune response. This regulatory mechanism also suggests that autoubiquitination, which is inherent to most single unit E3s in vitro, can function as a self-regulatory mechanism in vivo.

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“…For example, ELF4 expression could be induced following viral infection and then promote type I IFN expression and subsequent antiviral immune responses (20). Induction of deubiquitinase ubiquitin-specific protease 25 (USP25) by SeV or VSV infection could promote type I IFN expression by mediating the stabilization of TRAF3 and TRAF6 (21). By these means, host immune systems could eliminate invading viruses quickly and effectively.…”

Section: Discussionmentioning

confidence: 99%

Mint3 potentiates TLR3/4- and RIG-I–induced IFN-β expression and antiviral immune responses

Huai

Song

et al. 2016

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

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Type I IFNs (IFN-α/β) play crucial roles in the elimination of invading viruses. Multiple immune cells including macrophages recognize viral infection through a variety of pattern recognition receptors, such as Toll-like receptors (TLRs) and retinoic acid-inducible gene-I (RIG-I)-like receptors, and initiate type I IFN secretion and subsequent antiviral immune responses. However, the mechanisms by which host immune cells can produce adequate amounts of type I IFNs and then eliminate viruses effectively remain to be further elucidated. In the present study, we show that munc18-1-interacting protein 3 (Mint3) expression can be markedly induced during viral infection in macrophages. Mint3 enhances TLR3/4-and RIG-I-induced IRF3 activation and IFN-β production by promoting K63-linked polyubiquitination of TNF receptor-associated factor 3 (TRAF3). Consistently, Mint3 deficiency greatly attenuated antiviral immune responses and increased viral replication. Therefore, we have identified Mint3 as a physiological positive regulator of TLR3/4 and RIG-I-induced IFN-β production and have outlined a feedback mechanism for the control of antiviral immune responses.interferon | viral infection | TLR | RIG-I | TRAF3

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Induction of USP25 by viral infection promotes innate antiviral responses by mediating the stabilization of TRAF3 and TRAF6

Cited by 103 publications

References 39 publications

The Type I Interferon-IRF7 Axis Mediates Transcriptional Expression of Usp25 Gene

The Type I Interferon-IRF7 Axis Mediates Transcriptional Expression of Usp25 Gene

Changes in PUB22 Ubiquitination Modes Triggered by MITOGEN-ACTIVATED PROTEIN KINASE3 Dampen the Immune Response

Mint3 potentiates TLR3/4- and RIG-I–induced IFN-β expression and antiviral immune responses

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