Adenoviral E1A-associated protein p300 as a functional homologue of the transcriptional co-activator CBP

Nature. 1995 Mar 2;374(6517):85-8. doi: 10.1038/374085a0.


The 265K nuclear protein CBP was initially identified as a co-activator for the protein kinase A (PKA)-phosphorylated form of the transcription factor CREB. The domains in CBP that are involved in CREB binding and transcriptional activation are highly related to the adenoviral E1A-associated cellular protein p300 (refs 2, 3), and to two hypothetical proteins from Caenorhabditis elegans, R10E11.1 and K03H1.10 (refs 4 and 5, respectively), whose functions are unknown. Here, we show that CBP and p300 have similar binding affinity for the PKA-phosphorylated form of CREB, and that p300 can substitute for CBP in potentiating CREB-activated gene expression. We find that E1A binds to CBP through a domain conserved with p300 and represses the CREB-dependent co-activator functions of both CBP and p300. Our results indicate that the gene repression and cell immortalization functions associated with E1A involve the inactivation of a family of related proteins that normally participate in second-messenger-regulated gene expression.

Publication types

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

MeSH terms

  • Adenovirus E1A Proteins / metabolism*
  • Amino Acid Sequence
  • CREB-Binding Protein
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • E1A-Associated p300 Protein
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • Protein Binding
  • Sequence Homology, Amino Acid
  • Trans-Activators*
  • Transcription Factors / metabolism*
  • Transcriptional Activation*
  • Tumor Cells, Cultured


  • Adenovirus E1A Proteins
  • Cyclic AMP Response Element-Binding Protein
  • Nuclear Proteins
  • Trans-Activators
  • Transcription Factors
  • CREB-Binding Protein
  • E1A-Associated p300 Protein
  • Cyclic AMP-Dependent Protein Kinases