Bone morphogenetic protein 2 activates Smad6 gene transcription through bone-specific transcription factor Runx2.

Bone morphogenetic protein 2 activates Smad6 gene transcription through bone-specific transcription factor Runx2. Research Abstract Details 

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Bone morphogenetic protein 2 activates Smad6 gene transcription through bone-specific transcription factor Runx2. Abstract Text:

Qing Wang,Xiaochao Wei,Tianhui Zhu,Ming Zhang,Run Shen,Lianping Xing,Regis J O'Keefe,Di Chen,

BMP-2 plays an essential role in osteoblast and chondrocyte differentiation, but its signaling mechanism has not been fully defined. In the present studies, we investigated the mechanism through which BMP-2 activates the Smad6 gene. A -2006/+45 Smad6 promoter-luciferase construct was generated along with deletions and Runx2 binding site mutations to examine the role of Smad1 and Runx2 signaling following BMP-2 stimulation in osteoblasts. Transfection of Runx2 or treatment with BMP-2-stimulated promoter activity of the -2006/+45 and -1191/+45 reporters but not the -829/+45 and -374/+45 reporters. No Smad1/5 binding site is present in the -1191/-829 region of the Smad6 promoter. Mutation of the OSE2-a site (-1036/-1031) completely abolished the stimulatory effect of Runx2 as well as BMP-2 on the -2006/+45 and -1191/+45 Smad6 reporters. Gel shift and chromatin immunoprecipitation (ChIP) assays showed that Runx2 binds the OSE2-a element. ChIP assays demonstrated that Smad1 also interacts with the OSE2-a site at the Smad6 promoter through Runx2. The protein degradation of Runx2 is mediated by the E3 ubiquitin ligase Smurf1. In the present studies, we found that Smurf1 binds the OSE2-a site through Runx2 and inhibits Smad6 gene transcription. Treatment with BMP-2 and transfection of Smad1 abolished Smurf1 binding to the OSE2 site. These results show that Smad1 binding excludes Smurf1 interaction with the OSE2 site and promotes Smad6 gene transcription.

Bone morphogenetic protein 2 activates Smad6 gene transcription through bone-specific transcription factor Runx2. Publishing Authors By Initials

Q Wang,X Wei,T Zhu,M Zhang,R Shen,L Xing,RJ O'Keefe,D Chen,

For similar enzymes and coenzymes: enzymes: ligases: ubiquitin-protein ligase complexes: ubiquitin-protein ligases research abstracts see: enzymes and coenzymes: enzymes: ligases: ubiquitin-protein ligase complexes: ubiquitin-protein ligases research

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Bone morphogenetic protein 2 activates Smad6 gene transcription through bone-specific transcription factor Runx2. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 10742-8

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 10

MONTH: 01

YEAR: 2007

Bone morphogenetic protein 2 activates Smad6 gene transcription through bone-specific transcription factor Runx2. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Bone morphogenetic protein 2 activates Smad6 gene transcription through bone-specific transcription factor Runx2. Keywords Mesh Terms:

KEYWORDS: Ubiquitin-Protein Ligases

MESH TERMS: metabolism

Chemical & Substance for Abstract: Bone morphogenetic protein 2 activates Smad6 gene transcription through bone-specific transcription factor Runx2. Information

Substance Name: Ubiquitin-Protein Ligases

Registry Number: EC 6.3.2.19

Grant and Affiliation Information for Bone morphogenetic protein 2 activates Smad6 gene transcription through bone-specific transcription factor Runx2.

AFFILIATION: Medical College, Nankai University, Tianjin 300071, China.

Country: United States

AGENCY: United States NIAMS

GRANT: R01 AR051189

ACRONYM: AR

MEDLINETA: J Biol Chem

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