Skip to main content

Chromatin-bound p53 anchors activated Smads and the mSin3A corepressor to confer transforming-growth-factor-beta-mediated transcription repression.

Publication ,  Journal Article
Wilkinson, DS; Tsai, W-W; Schumacher, MA; Barton, MC
Published in: Mol Cell Biol
March 2008

In hepatic cells, Smad and SnoN proteins converge with p53 to repress transcription of AFP, an oncodevelopmental tumor marker aberrantly reactivated in hepatoma cells. Using p53- and SnoN-depleted hepatoma cell clones, we define a mechanism for repression mediated by this novel transcriptional partnership. We find that p53 anchors activated Smads and the corepressor mSin3A to the AFP distal promoter. Sequential chromatin immunoprecipitation analyses and molecular modeling indicate that p53 and Smad proteins simultaneously occupy overlapping p53 and Smad regulatory elements to establish repression of AFP transcription. In addition to its well-known function in antagonizing transforming growth factor beta (TGF-beta) responses, we find that SnoN actively participates in AFP repression by positively regulating mSin3A protein levels. We propose that activation of TGF-beta signaling restores a dynamic interplay between p53 and TGF-beta effectors that cooperate to effectively target mSin3A to tumor marker AFP and reestablish transcription repression.

Duke Scholars

Published In

Mol Cell Biol

DOI

EISSN

1098-5549

Publication Date

March 2008

Volume

28

Issue

6

Start / End Page

1988 / 1998

Location

United States

Related Subject Headings

  • alpha-Fetoproteins
  • Tumor Suppressor Protein p53
  • Transforming Growth Factor beta1
  • Transcription, Genetic
  • Smad4 Protein
  • Smad2 Protein
  • Sin3 Histone Deacetylase and Corepressor Complex
  • Signal Transduction
  • Repressor Proteins
  • Regulatory Sequences, Nucleic Acid
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wilkinson, D. S., Tsai, W.-W., Schumacher, M. A., & Barton, M. C. (2008). Chromatin-bound p53 anchors activated Smads and the mSin3A corepressor to confer transforming-growth-factor-beta-mediated transcription repression. Mol Cell Biol, 28(6), 1988–1998. https://doi.org/10.1128/MCB.01442-07
Wilkinson, Deepti Srinivas, Wen-Wei Tsai, Maria A. Schumacher, and Michelle Craig Barton. “Chromatin-bound p53 anchors activated Smads and the mSin3A corepressor to confer transforming-growth-factor-beta-mediated transcription repression.Mol Cell Biol 28, no. 6 (March 2008): 1988–98. https://doi.org/10.1128/MCB.01442-07.
Wilkinson, Deepti Srinivas, et al. “Chromatin-bound p53 anchors activated Smads and the mSin3A corepressor to confer transforming-growth-factor-beta-mediated transcription repression.Mol Cell Biol, vol. 28, no. 6, Mar. 2008, pp. 1988–98. Pubmed, doi:10.1128/MCB.01442-07.

Published In

Mol Cell Biol

DOI

EISSN

1098-5549

Publication Date

March 2008

Volume

28

Issue

6

Start / End Page

1988 / 1998

Location

United States

Related Subject Headings

  • alpha-Fetoproteins
  • Tumor Suppressor Protein p53
  • Transforming Growth Factor beta1
  • Transcription, Genetic
  • Smad4 Protein
  • Smad2 Protein
  • Sin3 Histone Deacetylase and Corepressor Complex
  • Signal Transduction
  • Repressor Proteins
  • Regulatory Sequences, Nucleic Acid