期刊
EXPERIMENTAL CELL RESEARCH
卷 262, 期 1, 页码 69-74出版社
ACADEMIC PRESS INC
DOI: 10.1006/excr.2000.5074
关键词
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Members of the transforming growth factor superfamily are known to transduce signals via the activation of Smad proteins. Ligand binding to transmembrane cell surface receptors triggers the phosphorylation of pathway-specific Smads. These Smads then complex with Smad 4 and are translocated to the nucleus where they effect gene transcription. Smads 1 and 4 were recently demonstrated to mediate BMP activation of the OPN promoter by inhibiting the interaction of Hoxc-8 protein with a Hox-binding element. While previous studies have indicated that specific DNA sequences are recognized by Smad complexes in several promoters, the role of Smad-binding elements (SBEs) in activation of the OPN promoter by members of the TGF beta superfamily has not been previously evaluated. In this study we tested the hypothesis that a putative Smad-binding region containing the sequence AGACTGTCTGGAC is involved in the activation of the OPN promoter by members of the TGF beta superfamily. Functional analyses demonstrated that the both the HBE- and Smad-binding region were involved in BMP-2-induced activation of the promoter, whereas, the HBE appeared to be the primary region involved in activation by TGF beta. Deletion of the first 9 bases in the Smad-binding region substantially reduced BMP-a-mediated activation of the promoter. These results strongly suggest that both the Hox- and the Smad-binding regions play a role in BMP-2-induced activation of the OPN promoter. (C) 2001 Academic Press.
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