期刊
CELLS TISSUES ORGANS
卷 189, 期 1-4, 页码 133-137出版社
KARGER
DOI: 10.1159/000151719
关键词
RUNX2; Transcriptional regulation; SMAD coregulatory proteins; BMP2 osteogenic signaling
资金
- NIAMS NIH HHS [R01 AR039588, R01 AR039588-11, R01 AR049069, AR39588] Funding Source: Medline
- NIA NIH HHS [R01 AG030228-02, R01 AG030228, AG030228] Funding Source: Medline
- NIDCR NIH HHS [DE12528, R01 DE012528, R01 DE012528-15, R37 DE012528, R56 DE012528] Funding Source: Medline
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR049069, R01AR039588] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH [R37DE012528] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH [R01DE012528] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R01AG030228] Funding Source: NIH RePORTER
BMP2 signaling and RUNX2 regulatory pathways converge for transcriptional control of bone formation in vivo. SMAD proteins are recruited to RUNX2 regulatory complexes via an overlapping nuclear matrix targeting signal/Smad interacting domain sequence (391-432) in Runx2. To establish the contribution of RUNX2-SMAD interaction to osteoblastogenesis, we characterized a number of point mutants. Only a triple mutation of amino acids 426-428 (HTY-AAA) results in loss of RUNX2 interactions with either BMP2- or TGF-beta-responsive SMADs and fails to integrate the BMP2/TGF-beta signal on target gene promoters. In a Runx2 null cell reconstitution assay, the HTY mutant did not activate the program of osteoblast differentiation ( alkaline phosphatase, collagen type 1, osteopontin, bone sialoprotein and osteocalcin) in response to BMP2 signaling. Thus, subnuclear targeting function and formation of a RUNX2- SMAD osteogenic complex are functionally inseparable. Taken together, these studies provide direct evidence that RUNX2 is essential for execution and completion of BMP2 signaling for osteoblast differentiation. Copyright (C) 2008 S. Karger AG, Basel
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据