Analysis of a cAMP-responsive activator reveals a two-component mechanism for transcriptional induction via signal-dependent factors

Genes Dev. 1997 Mar 15;11(6):738-47. doi: 10.1101/gad.11.6.738.

Abstract

We have examined the mechanism by which the cAMP-responsive factor CREB stimulates target gene expression following its phosphorylation at Ser-133. Using an in vitro transcription assay, we found that two signals were required for target gene activation: a phospho(Ser-133)-dependent interaction of CREB with RNA polymerase II via the coactivator CBP and a glutamine-rich domain interaction with TFIID via hTAF(II)130. The adenovirus E1A oncoprotein was found to inhibit phospho(Ser-133) CREB activity by binding to CBP and specifically blocking recruitment of RNA Pol II to the promoter. Our results suggest that the recruitment of CBP-RNA Pol II complexes per se is not sufficient for transcriptional activation and that activator-mediated recruitment of TFIID is additionally required for induction of signal-dependent genes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenovirus E1A Proteins / metabolism
  • Binding Sites
  • Cyclic AMP / metabolism
  • Cyclic AMP Response Element-Binding Protein / chemistry
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Escherichia coli / genetics
  • HeLa Cells
  • Humans
  • Phosphorylation
  • RNA Polymerase II / metabolism
  • Signal Transduction
  • Transcription Factor TFIID
  • Transcription Factors, TFII / metabolism
  • Transcriptional Activation

Substances

  • Adenovirus E1A Proteins
  • Cyclic AMP Response Element-Binding Protein
  • Transcription Factor TFIID
  • Transcription Factors, TFII
  • Cyclic AMP
  • RNA Polymerase II