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MAP kinase phosphatase-1 expression is regulated by 15-deoxy-Δ12,14-prostaglandin J2 via a HuR-dependent post-transcriptional mechanism.

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dc.contributor.authorWoo, JH-
dc.contributor.authorLee, JH-
dc.contributor.authorKim, H-
dc.contributor.authorChoi, Y-
dc.contributor.authorPark, SM-
dc.contributor.authorJoe, EH-
dc.contributor.authorJou, I-
dc.date.accessioned2017-04-04T05:28:46Z-
dc.date.available2017-04-04T05:28:46Z-
dc.date.issued2015-
dc.identifier.issn0006-3002-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/13761-
dc.description.abstractIn the present study, we demonstrate a mechanism through which 15-deoxy-Δ(12,14)-prostaglandin J2 (15d-PGJ2) induces MKP-1 expression in rat primary astrocytes, leading to the regulation of inflammatory responses. We show that 15d-PGJ2 enhances the efficiency of MKP-1 pre-mRNA processing (constitutive splicing and 3'-end processing) and increases the stability of the mature mRNA. We further report that this occurs via the RNA-binding protein, Hu antigen R (HuR). Our experiments show that HuR knockdown abrogates the 15d-PGJ2-induced increases in the pre-mRNA processing and mature mRNA stability of MKP-1, whereas HuR overexpression further enhances the 15d-PGJ2-induced increases in these parameters. Using cysteine (Cys)-mutated HuR proteins, we show that the Cys-245 residue of HuR (but not Cys-13 or Cys-284) is critical for the direct binding of HuR with 15d-PGJ2 and the effects downstream of this interaction. Collectively, our data show that HuR is a novel target of 15d-PGJ2 and reveal HuR-mediated pre-mRNA processing and mature mRNA stabilization as important regulatory steps in the 15d-PGJ2-induced expression of MKP-1. The potential to use a small molecule such as 15d-PGJ2 to regulate the induction of MKP-1 at multiple levels of gene expression could be exploited as a novel therapeutic strategy aimed at combating a diverse range of MKP-1-associated pathologies.-
dc.language.isoen-
dc.subject.MESHAnimals-
dc.subject.MESHAstrocytes-
dc.subject.MESHDual Specificity Phosphatase 1-
dc.subject.MESHELAV Proteins-
dc.subject.MESHGene Expression Regulation-
dc.subject.MESHInflammation-
dc.subject.MESHPrimary Cell Culture-
dc.subject.MESHProstaglandin D2-
dc.subject.MESHRNA Precursors-
dc.subject.MESHRNA Processing, Post-Transcriptional-
dc.subject.MESHRNA Stability-
dc.subject.MESHRNA, Messenger-
dc.subject.MESHRats-
dc.titleMAP kinase phosphatase-1 expression is regulated by 15-deoxy-Δ12,14-prostaglandin J2 via a HuR-dependent post-transcriptional mechanism.-
dc.typeArticle-
dc.identifier.pmid25805336-
dc.identifier.urlhttps://linkinghub.elsevier.com/retrieve/pii/S1874-9399(15)00069-3-
dc.contributor.affiliatedAuthor우, 주홍-
dc.contributor.affiliatedAuthor이, 지훈-
dc.contributor.affiliatedAuthor박, 상면-
dc.contributor.affiliatedAuthor조, 은혜-
dc.contributor.affiliatedAuthor주, 일로-
dc.type.localJournal Papers-
dc.identifier.doi10.1016/j.bbagrm.2015.03.004-
dc.citation.titleBiochimica et biophysica acta-
dc.citation.volume1849-
dc.citation.number6-
dc.citation.date2015-
dc.citation.startPage612-
dc.citation.endPage625-
dc.identifier.bibliographicCitationBiochimica et biophysica acta, 1849(6). : 612-625, 2015-
dc.identifier.eissn1878-2434-
dc.relation.journalidJ000063002-
Appears in Collections:
Journal Papers > Research Organization > Inflamm-aging Translational Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
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