Role of p300, a transcriptional coactivator, in signalling of TGF-beta

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A Nishihara1, J I Hanai, N Okamoto

  • 1Department of Biochemistry, The Cancer Institute, Japanese Foundation for Cancer Research (JFCR), and Research for the Future Program, Japan.

Genes to Cells : Devoted to Molecular & Cellular Mechanisms
|November 13, 1998
PubMed
Abstract

Insights

p300 protein enhances transforming growth factor-beta (TGF-beta) signaling by interacting with Smad proteins. This interaction is crucial for Smad-mediated gene transcription and is inhibited by adenoviral E1A protein.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Transcriptional Regulation

Background:

  • Smad proteins are key mediators of transforming growth factor-beta (TGF-beta) superfamily signaling.
  • p300/CBP act as coactivators for transcription factors through direct interactions.
  • Adenoviral oncoprotein E1A inhibits TGF-beta signaling by binding to p300, suggesting p300's role in this pathway.

Purpose of the Study:

  • To investigate the involvement of p300 in Smad-mediated transcriptional activation.
  • To elucidate the interaction between p300 and Smad proteins in TGF-beta signaling.

Main Methods:

  • Assessed p300's effect on Smad-induced transactivation using the p3TP-Lux reporter assay.
  • Investigated the interaction between p300 and Smad proteins in vivo.
  • Mapped the binding regions of Smad3 and p300 involved in their interaction.
  • Utilized dominant-negative constructs to assess the functional impact of p300-Smad interaction.

Main Results:

  • p300 significantly enhanced Smad-induced transactivation of the TGF-beta responsive reporter.
  • Adenoviral E1A inhibited p300's enhancement of Smad activity, dependent on E1A's p300-binding capability.
  • p300 directly interacted with Smad2 and Smad3 in a ligand-dependent manner.
  • Specific binding regions were identified in Smad3 (C-terminal half) and p300 (C-terminal 678 amino acids).
  • Dominant-negative inhibition of p300-Smad interaction impaired transactivation.

Conclusions:

  • p300 interacts with Smad2 and Smad3 in a ligand-dependent manner.
  • p300 enhances Smad-mediated transactivation, providing molecular insights into Smad protein function.

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