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BMP2-activated Erk/MAP kinase stabilizes runx2 by increasing p300 levels and histone acetyltransferase activity

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dc.contributor.authorJun, Ji Hae-
dc.contributor.authorYoon, Won-Joon-
dc.contributor.authorSeo, Sang-Beom-
dc.contributor.authorWoo, Kyung-Mi-
dc.contributor.authorKim, Gwan-Shik-
dc.contributor.authorRyoo, Hyun-Mo-
dc.contributor.authorBaek, Jeong-Hwa-
dc.date.accessioned2011-10-13T07:54:20Z-
dc.date.available2011-10-13T07:54:20Z-
dc.date.issued2010-11-
dc.identifier.citationJournal of Biological Chemistry 285,36410-36419en
dc.identifier.issn0021-9258-
dc.identifier.urihttp://hdl.handle.net/10371/74114-
dc.description.abstractRunx2 is a critical transcription factor for osteoblast differentiation. Regulation of Runx2 expression levels and transcriptional activity is important for bone morphogenetic protein (BMP)-induced osteoblast differentiation. Previous studies have shown that extracellular signal-regulated kinase (Erk) activation enhances the transcriptional activity of Runx2 and that BMP-induced Runx2 acetylation increases Runx2 stability and transcriptional activity. Because BMP signaling induces Erk activation in osteoblasts, we sought to investigate whether BMP-induced Erk signaling regulates Runx2 acetylation and stability. Erk activation by overexpression of constitutively active MEK1 increased Runx2 transcriptional activity, whereas U0126, an inhibitor of MEK1/2, suppressed basal Runx2 transcriptional activity and BMP-induced Runx2 acetylation and stabilization. Overexpression of constitutively active MEK1 stabilized Runx2 protein via up-regulation of acetylation and down-regulation of ubiquitination. Erk activation increased p300 protein levels and histone acetyltransferase activity. Knockdown of p300 using siRNA diminished Erk-induced Runx2 stabilization. Overexpression of Smad5 increased Runx2 acetylation and stabilization. Erk activation further increased Smad-induced Runx2 acetylation and stabilization, whereas U0126 suppressed these functions. On the other hand, knockdown of Smad1 and Smad5 by siRNA suppressed both basal and Erk-induced Runx2 protein levels. Erk activation enhanced the association of Runx2 with p300 and Smad1. Taken together these results indicate that Erk signaling increases Runx2 stability and transcriptional activity, partly via increasing p300 protein levels and histone acetyltransferase activity and subsequently increasing Runx2 acetylation by p300. In addition to the canonical Smad pathway, a BMP-induced non-Smad Erk signaling pathway cooperatively regulates osteoblast differentiation partly via increasing the stability and transcriptional activity of Runx2.en
dc.description.sponsorshipThis work was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology(Grants 311-2006-1-E00093 and 531-2007-1-E00070) and by the Korea Health 21 R&D Project, Ministry of Health and Welfare(Grant A085021).en
dc.language.isoenen
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen
dc.titleBMP2-activated Erk/MAP kinase stabilizes runx2 by increasing p300 levels and histone acetyltransferase activityen
dc.typeArticleen
dc.contributor.AlternativeAuthor전지해-
dc.contributor.AlternativeAuthor윤원준-
dc.contributor.AlternativeAuthor서상범-
dc.contributor.AlternativeAuthor우경미-
dc.contributor.AlternativeAuthor김관식-
dc.contributor.AlternativeAuthor류현모-
dc.contributor.AlternativeAuthor백정화-
dc.identifier.doi10.1074/jbc.M110.142307-
Appears in Collections:
College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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