Dual-specificity phosphatase 5 acts as an anti-inflammatory regulator by inhibiting the ERK and NF-kappa B signaling pathways
DC Field | Value | Language |
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dc.contributor.author | Seo, Huiyun | - |
dc.contributor.author | Cho, Young-Chang | - |
dc.contributor.author | Ju, Anna | - |
dc.contributor.author | Lee, Sewoong | - |
dc.contributor.author | Park, Byoung Chul | - |
dc.contributor.author | Park, Sung Goo | - |
dc.contributor.author | Kim, Jeong-Hoon | - |
dc.contributor.author | Kim, Kwonseop | - |
dc.contributor.author | Cho, Sayeon | - |
dc.date.available | 2019-03-08T07:36:03Z | - |
dc.date.issued | 2017-12 | - |
dc.identifier.issn | 2045-2322 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/3503 | - |
dc.description.abstract | Although dual-specificity phosphatase 5 (DUSP5), which inactivates extracellular signal-regulated kinase (ERK), suppresses tumors in several types of cancer, its functional roles remain largely unknown. Here, we show that DUSP5 is induced during lipopolysaccharide (LPS)-mediated inflammation and inhibits nuclear factor-kappa B (NF-kappa B) activity. DUSP5 mRNA and protein expression increased transiently in LPS-stimulated RAW 264.7 cells and then returned to basal levels. DUSP5 overexpression in RAW 264.7 cells suppressed the production of pro-inflammatory tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), whereas knockdown of DUSP5 increased their expression. Investigation of two major inflammatory signaling pathways, mitogen-activated protein kinase (MAPK) and NF-kappa B, using activator protein-1 (AP-1) and NF-kappa B reporter plasmids, respectively, showed that NF-kappa B transcription activity was downregulated by DUSP5 in a phosphatase activity-independent manner whereas AP-1 activity was inhibited by DUSP5 phosphatase activity towards ERK,. Further investigation showed that DUSP5 directly interacts with transforming growth factor beta-activated kinase 1 (TAK1) and inhibitor of.B (I kappa B) kinases (IKKs) but not with I kappa Ba. DUSP5 binding to IKKs interfered with the association of TAK1 with IKKs, suggesting that DUSP5 might act as a competitive inhibitor of TAK1-IKKs association. Therefore, we propose that DUSP5 negatively regulates ERK and NF-kappa B in a phosphatase activitydependent and -independent manner, respectively. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.title | Dual-specificity phosphatase 5 acts as an anti-inflammatory regulator by inhibiting the ERK and NF-kappa B signaling pathways | - |
dc.type | Article | - |
dc.identifier.doi | 10.1038/s41598-017-17591-9 | - |
dc.identifier.bibliographicCitation | SCIENTIFIC REPORTS, v.7, no.1 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000417570500067 | - |
dc.identifier.scopusid | 2-s2.0-85041794328 | - |
dc.citation.number | 1 | - |
dc.citation.title | SCIENTIFIC REPORTS | - |
dc.citation.volume | 7 | - |
dc.type.docType | Article | - |
dc.publisher.location | 영국 | - |
dc.subject.keywordPlus | LIPOPOLYSACCHARIDE-STIMULATED MACROPHAGES | - |
dc.subject.keywordPlus | PROTEIN-KINASE PHOSPHATASE-1 | - |
dc.subject.keywordPlus | TNF-ALPHA PRODUCTION | - |
dc.subject.keywordPlus | MAP KINASE | - |
dc.subject.keywordPlus | IMMUNE-RESPONSES | - |
dc.subject.keywordPlus | INNATE IMMUNITY | - |
dc.subject.keywordPlus | TYROSINE PHOSPHATASES | - |
dc.subject.keywordPlus | POSITIVE REGULATION | - |
dc.subject.keywordPlus | PHOSPHORYLATION | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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