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Adenovirus DNA binding protein inhibits SrCap-activated CBP and CREB-mediated transcription

Xiequn Xu1, Vera Tarakanova, John Chrivia

  • 1Department of Molecular Microbiology and Immunology, Saint Louis University Health Sciences Center, Saint Louis, MO 63104, USA.

Virology
|September 5, 2003
PubMed

Insights

Adenovirus 2 DNA Binding Protein (DBP) inhibits transcription mediated by SNF2-related CBP activator protein (SrCap). DBP specifically blocks SrCap

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Transcription Factors

Background:

  • SNF2-related CBP activator protein (SrCap) is a key mediator of transcription involving CBP and CREB.
  • Adenovirus 2 DNA Binding Protein (DBP) has been shown to bind SrCap and inhibit its carboxyl-terminal activity.

Purpose of the Study:

  • To investigate the effect of DBP on the transcriptional activity of full-length SrCap.
  • To determine if DBP's inhibitory effect on SrCap is specific.

Main Methods:

  • Assessed the impact of DBP on SrCap-mediated transcription using Gal-CREB and Gal-CBP systems.
  • Evaluated DBP's effect on Protein Kinase A (PKA)-activated transcription of the enkephalin promoter.
  • Utilized a mammalian two-hybrid system to examine DBP's inhibition of SrCap-CBP interactions.
  • Tested DBP's effect on a non-SrCap-related transcriptional activator to assess specificity.

Main Results:

  • DBP significantly inhibits the transcriptional activation mediated by full-length SrCap.
  • DBP suppresses PKA-activated transcription of the enkephalin promoter via SrCap.
  • DBP dramatically inhibits transcription in a mammalian two-hybrid system dependent on SrCap-CBP interaction.
  • DBP's inhibitory effect is specific to SrCap, as it does not affect unrelated transcriptional activators.

Conclusions:

  • DBP acts as a specific inhibitor of SrCap-mediated transcription.
  • The findings support a model where DBP interferes with the SrCap-CBP interaction to inhibit cellular transcription.

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