TRAF6-mediated ubiquitination of MST1/STK4 attenuates the TLR4-NF-kappa B signaling pathway in macrophages

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dc.contributor.authorRoh, Kyung-Hyeko
dc.contributor.authorLee, Yeojinko
dc.contributor.authorYoon, Je-Hyunko
dc.contributor.authorLee, Danbiko
dc.contributor.authorKim, Eunjuko
dc.contributor.authorPark, Eunchongko
dc.contributor.authorLee, In Youngko
dc.contributor.authorKim, Tae Sungko
dc.contributor.authorSong, Hyun Kyuko
dc.contributor.authorShin, Jaekyoonko
dc.contributor.authorLim, Dae-Sikko
dc.contributor.authorChoi, Eui-Juko
dc.date.accessioned2021-03-30T05:30:09Z-
dc.date.available2021-03-30T05:30:09Z-
dc.date.created2020-10-13-
dc.date.issued2021-03-
dc.identifier.citationCELLULAR AND MOLECULAR LIFE SCIENCES, v.78, no.5, pp.2315 - 2328-
dc.identifier.issn1420-682X-
dc.identifier.urihttp://hdl.handle.net/10203/282229-
dc.description.abstractPattern-recognition receptors including Toll-like receptors (TLRs) recognize invading pathogens and trigger an immune response in mammals. Here we show that mammalian ste20-like kinase 1/serine/threonine kinase 4 (MST1/STK4) functions as a negative regulator of lipopolysaccharide (LPS)-induced activation of the TLR4-NF-kappa B signaling pathway associated with inflammation. Myeloid-specific genetic ablation of MST1/STK4 increased the susceptibility of mice to LPS-induced septic shock. Ablation of MST1/STK4 also enhanced NF-kappa B activation triggered by LPS in bone marrow-derived macrophages (BMDMs), leading to increased production of proinflammatory cytokines by these cells. Furthermore, MST1/STK4 inhibited TRAF6 autoubiquitination as well as TRAF6-mediated downstream signaling induced by LPS. In addition, we found that TRAF6 mediates the LPS-induced activation of MST1/STK4 by catalyzing its ubiquitination, resulting in negative feedback regulation by MST1/STK4 of the LPS-induced pathway leading to cytokine production in macrophages. Together, our findings suggest that MST1/STK4 functions as a negative modulator of the LPS-induced NF-kappa B signaling pathway during macrophage activation.-
dc.languageEnglish-
dc.publisherSPRINGER BASEL AG-
dc.titleTRAF6-mediated ubiquitination of MST1/STK4 attenuates the TLR4-NF-kappa B signaling pathway in macrophages-
dc.typeArticle-
dc.identifier.wosid000572730100001-
dc.identifier.scopusid2-s2.0-85091409057-
dc.type.rimsART-
dc.citation.volume78-
dc.citation.issue5-
dc.citation.beginningpage2315-
dc.citation.endingpage2328-
dc.citation.publicationnameCELLULAR AND MOLECULAR LIFE SCIENCES-
dc.identifier.doi10.1007/s00018-020-03650-4-
dc.contributor.localauthorLim, Dae-Sik-
dc.contributor.nonIdAuthorRoh, Kyung-Hye-
dc.contributor.nonIdAuthorLee, Yeojin-
dc.contributor.nonIdAuthorYoon, Je-Hyun-
dc.contributor.nonIdAuthorLee, Danbi-
dc.contributor.nonIdAuthorKim, Eunju-
dc.contributor.nonIdAuthorPark, Eunchong-
dc.contributor.nonIdAuthorLee, In Young-
dc.contributor.nonIdAuthorKim, Tae Sung-
dc.contributor.nonIdAuthorSong, Hyun Kyu-
dc.contributor.nonIdAuthorShin, Jaekyoon-
dc.contributor.nonIdAuthorChoi, Eui-Ju-
dc.description.isOpenAccessN-
dc.type.journalArticleArticle-
dc.subject.keywordAuthorLipopolysaccharides-
dc.subject.keywordAuthorMST1/STK4-
dc.subject.keywordAuthorNF-kappa B-
dc.subject.keywordAuthorTRAF6-
dc.subject.keywordPlusNF-KAPPA-B-
dc.subject.keywordPlusINTERACTING PROTEIN P62-
dc.subject.keywordPlusNEGATIVE REGULATION-
dc.subject.keywordPlusIMPORTANT MEDIATOR-
dc.subject.keywordPlusMST1 KINASE-
dc.subject.keywordPlusADAPTER P62-
dc.subject.keywordPlusACTIVATION-
dc.subject.keywordPlusRECEPTOR-
dc.subject.keywordPlusTRAF6-
dc.subject.keywordPlusIDENTIFICATION-
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