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We are analyzing https://www.nature.com/articles/ni.2427.

Title:
Negative regulation of IL-17-mediated signaling and inflammation by the ubiquitin-specific protease USP25 | Nature Immunology
Description:
How IL-17 signaling is regulated remains poorly understood. Dong and colleagues identify the ubiquitin-specific protease USP25 as a negative regulator of IL-17-mediated signaling and inflammation. Interleukin 17 (IL-17) is important in infection and autoimmunity; how it signals remains poorly understood. In this study, we identified the ubiquitin-specific protease USP25 as a negative regulator of IL-17-mediated signaling and inflammation. Overexpression of USP25 inhibited IL-17-triggered signaling, whereas USP25 deficiency resulted in more phosphorylation of the inhibitor IκBα and kinase Jnk and higher expression of chemokines and cytokines, as well as a prolonged half-life for chemokine CXCL1–encoding mRNA after treatment with IL-17. Consistent with that, Usp25−/− mice showed greater sensitivity to IL-17-dependent inflammation and autoimmunity in vivo. Mechanistically, stimulation with IL-17 induced the association of USP25 with the adaptors TRAF5 and TRAF6, and USP25 induced removal of Lys63-linked ubiquitination in TRAF5 and TRAF6 mediated by the adaptor Act1. Thus, our results demonstrate that USP25 is a deubiquitinating enzyme (DUB) that negatively regulates IL-17-triggered signaling.
Website Age:
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pubmed, google, scholar, cas, nature, signaling, central, immunol, usp, cells, inflammation, interleukin, article, traf, nat, wang, content, dong, access, activation, regulation, ubiquitinspecific, liu, chen, cell, biol, ubiquitin, cookies, chang, kinase, ubiquitination, adaptor, act, immunity, required, receptor, privacy, immunology, protease, zhong, deubiquitinating, enzyme, family, responses, signal, chem, sci, nfκb, factor, center,

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nature portfolio permissions reprints privacy policy research il-1β-triggered nf-κb activation il-17ra/il-17rc receptor complex interleukin-1β-induced ikk/nf-κb advertising ubiquitous nature rig-i-mediated antiviral activity social media author information authors nature 412 nature 461 nature 446 nature ubiquitin-specific protease usp25 nf-κb regulatory pathways nf-κb inhibitor a20 splicing-regulatory factor sf2 ubiquitin-specific deubiquitinating enzymes ubiquitin-modifying enzyme a20 gene-poor region 21q11 author correspondence nf-κb signaling pathway ubiquitin-specific protease 28 chemokine cxcl1–encoding mrna il-17f-dependent signaling personal data scfβ-trcp-mediated degradation plasmids encoding traf1–traf6 innate il-17-producing cells data protection springerlink instant access virus-triggered signaling permissions nf-κb pathway virus-triggered ubiquitination usp25 induced removal t-helper-cell lineages iκb kinase complex ubiquitin-dependent kinase ubiquitin replacement strategy hemagglutinin-tagged ubiquitin seon hee chang chemokine cxcl1 mrna privacy iκb kinase activation experimental autoimmune encephalomyelitis cellular antiviral response

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      headline:Negative regulation of IL-17-mediated signaling and inflammation by the ubiquitin-specific protease USP25
      description:How IL-17 signaling is regulated remains poorly understood. Dong and colleagues identify the ubiquitin-specific protease USP25 as a negative regulator of IL-17-mediated signaling and inflammation. Interleukin 17 (IL-17) is important in infection and autoimmunity; how it signals remains poorly understood. In this study, we identified the ubiquitin-specific protease USP25 as a negative regulator of IL-17-mediated signaling and inflammation. Overexpression of USP25 inhibited IL-17-triggered signaling, whereas USP25 deficiency resulted in more phosphorylation of the inhibitor IκBα and kinase Jnk and higher expression of chemokines and cytokines, as well as a prolonged half-life for chemokine CXCL1–encoding mRNA after treatment with IL-17. Consistent with that, Usp25−/− mice showed greater sensitivity to IL-17-dependent inflammation and autoimmunity in vivo. Mechanistically, stimulation with IL-17 induced the association of USP25 with the adaptors TRAF5 and TRAF6, and USP25 induced removal of Lys63-linked ubiquitination in TRAF5 and TRAF6 mediated by the adaptor Act1. Thus, our results demonstrate that USP25 is a deubiquitinating enzyme (DUB) that negatively regulates IL-17-triggered signaling.
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         Infectious Diseases
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