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Gadd45β is transcriptionally activated by p53 via p38α-mediated phosphorylation during myocardial ischemic injury.

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dc.contributor.authorKim, YA-
dc.contributor.authorKim, MY-
dc.contributor.authorYu, HY-
dc.contributor.authorMishra, SK-
dc.contributor.authorLee, JH-
dc.contributor.authorChoi, KS-
dc.contributor.authorKim, JH-
dc.contributor.authorXiang, YK-
dc.contributor.authorJung, YS-
dc.date.accessioned2014-04-30-
dc.date.available2014-04-30-
dc.date.issued2013-
dc.identifier.issn0946-2716-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/9867-
dc.description.abstractGrowth arrest and DNA damage-inducible 45β (Gadd45β) have been shown to play a role in inducing cardiomyocyte apoptosis under ischemia/anoxia. The well-known transcription factor p53 is known to cause apoptosis in cardiomyocytes under ischemia. Based on the common role of Gadd45β and p53 in ischemia-induced apoptosis, we investigated whether p53 is involved in the mechanisms responsible for Gadd45β expression in both in vitro and in vivo models of ischemic heart injury. A chromatin immunoprecipitation assay revealed direct binding of p53 to the Gadd45β promoter region during anoxia, and this binding was confirmed by surface plasmon resonance imaging. In rat heart-derived H9c2 cells, silencing of p53 abrogated the increase of Gadd45β promoter-luciferase reporter (Gadd45β-Luc) activity and the expression of Gadd45β under anoxia and overexpression of p53 enhanced Gadd45β-Luc activity and Gadd45β expression. Gadd45β mRNA and protein expression were significantly inhibited by p53 siRNA in a rat ischemic heart model. In addition, p38α-mediated phophorylation of p53 at both Ser15 and Ser20 was shown to be essential for the expression of Gadd45β mRNA and protein during anoxia. These results reveal the p38α-p53-Gadd45β axis as a novel signaling module in the anoxia-induced apoptotic death pathway. In conclusion, this study provides molecular evidence that Gadd45β is a novel downstream target gene of p53 under ischemia/anoxia and suggests the therapeutic potential of targeting Gadd45β as a treatment of ischemic heart injury.-
dc.language.isoen-
dc.titleGadd45β is transcriptionally activated by p53 via p38α-mediated phosphorylation during myocardial ischemic injury.-
dc.typeArticle-
dc.identifier.pmid23948959-
dc.contributor.affiliatedAuthor최, 경숙-
dc.type.localJournal Papers-
dc.identifier.doi10.1007/s00109-013-1070-9-
dc.citation.titleJournal of molecular medicine (Berlin, Germany)-
dc.citation.volume91-
dc.citation.number11-
dc.citation.date2013-
dc.citation.startPage1303-
dc.citation.endPage1313-
dc.identifier.bibliographicCitationJournal of molecular medicine (Berlin, Germany), 91(11). : 1303-1313, 2013-
dc.identifier.eissn1432-1440-
dc.relation.journalidJ009462716-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
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