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Functional analysis of the transforming growth factor beta responsive elements in the WAF1/Cip1/p21 promoter.

Publication ,  Journal Article
Datto, MB; Yu, Y; Wang, XF
Published in: J Biol Chem
December 1, 1995

The transforming growth factor beta s (TGF-beta s) are a group of multifunctional growth factors that inhibit cell cycle progression in many cell types. The TGF-beta-induced cell cycle arrest has been partially attributed to the regulatory effects of TGF-beta on both the levels and activities of the G1 cyclins and their cyclin-dependent kinase partners. The ability of TGF-beta to inhibit the activity of these kinase complexes derives in part from its regulatory effects on the cyclin-dependent kinase inhibitors, p21/WAF1/Cip1, p27Kip1, and p15. Upon treatment of cells with TGF-beta, these three inhibitors bind to and block the activities of specific cyclin-cyclin-dependent kinase complexes to cause cell cycle arrest. Little is known, however, on the mechanism through which TGF-beta activates these cyclin-dependent kinase inhibitors. In the case of p21, TGF-beta treatment leads to an increase in p21 mRNA. This increase in p21 mRNA is partly due to transcriptional activation of the p21 promoter by TGF-beta. To further define the signaling pathways through which TGF-beta induces p21, we have performed a detailed functional analysis on the p21 promoter. Through both deletion and mutation analysis of the p21 promoter, we have defined a 10-base pair sequence that is required for the activation of the p21 promoter by TGF-beta. In addition, this sequence is sufficient to drive TGF-beta-mediated transcription from a previously nonresponsive promoter. Preliminary gel shift assays demonstrate that this TGF-beta responsive element binds specifically to several proteins in vitro. Two of these proteins are the transcription factors Sp-1 and Sp-3. These studies represent the initial steps toward defining the signaling pathways involved in TGF-beta-mediated transcriptional activation of p21.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

December 1, 1995

Volume

270

Issue

48

Start / End Page

28623 / 28628

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Transcription, Genetic
  • Sequence Deletion
  • Proteins
  • Promoter Regions, Genetic
  • Oligodeoxyribonucleotides
  • Molecular Sequence Data
  • Humans
  • DNA Mutational Analysis
  • Cyclins
 

Citation

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Datto, M. B., Yu, Y., & Wang, X. F. (1995). Functional analysis of the transforming growth factor beta responsive elements in the WAF1/Cip1/p21 promoter. J Biol Chem, 270(48), 28623–28628. https://doi.org/10.1074/jbc.270.48.28623
Datto, M. B., Y. Yu, and X. F. Wang. “Functional analysis of the transforming growth factor beta responsive elements in the WAF1/Cip1/p21 promoter.J Biol Chem 270, no. 48 (December 1, 1995): 28623–28. https://doi.org/10.1074/jbc.270.48.28623.
Datto, M. B., et al. “Functional analysis of the transforming growth factor beta responsive elements in the WAF1/Cip1/p21 promoter.J Biol Chem, vol. 270, no. 48, Dec. 1995, pp. 28623–28. Pubmed, doi:10.1074/jbc.270.48.28623.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

December 1, 1995

Volume

270

Issue

48

Start / End Page

28623 / 28628

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Transcription, Genetic
  • Sequence Deletion
  • Proteins
  • Promoter Regions, Genetic
  • Oligodeoxyribonucleotides
  • Molecular Sequence Data
  • Humans
  • DNA Mutational Analysis
  • Cyclins