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A functional interaction with CBP contributes to transcriptional activation by the Wilms tumor suppressor WT1

W Wang1, S B Lee, R Palmer

  • 1Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts 02129, USA.

The Journal of Biological Chemistry
|March 30, 2001
PubMed

Insights

The Wilms tumor gene (WT1) acts as a transcriptional activator, not a repressor, by interacting with the coactivator CBP. This interaction is crucial for activating genes essential for cellular differentiation.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Genetics

Background:

  • The Wilms tumor gene (WT1) encodes a transcription factor vital for kidney development.
  • WT1 was initially characterized as a transcriptional repressor, but recent evidence suggests it can also activate gene expression.

Purpose of the Study:

  • To investigate the mechanism by which WT1 regulates gene transcription.
  • To determine if WT1 interacts with transcriptional coactivators to mediate gene activation.

Main Methods:

  • In vitro and in vivo binding assays to confirm WT1-CBP interaction.
  • Co-immunoprecipitation from embryonic rat kidney cells.
  • Reporter gene assays and retroviral expression studies in human hematopoietic cells to assess functional consequences.

Main Results:

  • WT1 physically interacts with the transcriptional coactivator CBP.
  • This interaction synergistically activates a physiologically relevant promoter.
  • Specific domains of WT1 and CBP are required for this association.
  • Inhibition of the WT1-CBP interaction suppresses WT1-mediated activation of the p21(Cip1) gene.

Conclusions:

  • WT1 functions as a transcriptional activator for genes involved in cellular differentiation.
  • The interaction with CBP is a key mechanism for WT1-mediated transcriptional activation.

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