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A novel transcriptional repression domain mediates p21(WAF1/CIP1) induction of p300 transactivation

A W Snowden1, L A Anderson, G A Webster

  • 1Division of Gene Regulation and Expression, Department of Biochemistry, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom.

Molecular and Cellular Biology
|March 25, 2000
PubMed

Insights

The cell cycle regulator p21(WAF/CIP1) enhances the activity of transcriptional coactivators p300 and CREB binding protein (CBP). This occurs via a novel repression domain (CRD1), independent of histone acetyltransferase activity.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • p300 and CREB binding protein (CBP) are crucial transcriptional coactivators regulating cell cycle, differentiation, and tumorigenesis.
  • These proteins are implicated in cancer, targeted by viral oncoproteins, and interact with key factors like p53 and E2F.
  • p300 dysfunction leads to cellular proliferation defects.

Purpose of the Study:

  • To investigate the mechanism by which p21(WAF/CIP1) influences the transcriptional activity of p300 and CBP.
  • To identify novel regulatory domains and interactions involved in p300/CBP function.

Main Methods:

  • Coexpression of p21(WAF/CIP1) with p300 and CBP.
  • Assays to measure transcriptional activation.
  • Analysis of histone acetyltransferase (HAT) activity.
  • Characterization of a novel transcriptional repression domain (CRD1).

Main Results:

  • p21(WAF/CIP1) significantly stimulates transcriptional activation by p300 and CBP.
  • This stimulation is independent of the intrinsic HAT activity and the cyclinE-Cdk2 binding site of p300/CBP.
  • A previously uncharacterized transcriptional repression domain (CRD1) in p300 was identified.
  • p21 enhances p300 activity by relieving repression mediated by CRD1.
  • The regulation of CRD1 by p21 is promoter-dependent.

Conclusions:

  • p21(WAF/CIP1) acts as a novel regulator of p300 and CBP activity through the CRD1 domain.
  • This mechanism provides a new way for p300/CBP to modulate gene expression, switching between growth promotion and cell cycle arrest.
  • The findings offer insights into the complex regulation of cell growth and cancer development.

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