Inhibition of p53-mediated transactivation and cell cycle arrest by E1A through its p300/CBP-interacting region

Oncogene. 1997 Mar 6;14(9):1047-57. doi: 10.1038/sj.onc.1201002.


Cellular transformation by the adenovirus E1A oncoprotein requires its p300/CBP- and Rb-binding domains. We mapped inhibition of p53-mediated transactivation to the p300/CBP-binding region of E1A. An E1A mutant incapable of physically interacting with Rb retained the capacity to inhibit transactivation by p53, whereas E1A mutants of the p300/CBP-interacting domain failed to inhibit p53. The inhibitory effect of the p300/CBP-binding region of E1A on p53 was demonstrated with p53-activated reporters and endogenous p53 targets such as p21(WAF1/CIP1) or MDM2. E1A lacking the capacity to interact with Rb, but capable of p300/CBP interaction, was competent in suppression of a DNA-damage activated p53-dependent cell cycle checkpoint. Exogenous CBP and p300 were able to individually relieve E1A's inhibitory effect on p53-mediated transcription. Mutants of E1A that are not capable of interacting with p300 or CBP were found to efficiently stabilize endogenous p53 but were not competent in repression of p21 expression thus dissociating these two effects of E1A. Our results suggest that the p300/CBP-binding domain of E1A inhibits a p53-dependent cellular response which normally inhibits DNA replication following Adenovirus infection.

MeSH terms

  • Acetyltransferases*
  • Adenovirus E1A Proteins / drug effects
  • Adenovirus E1A Proteins / genetics*
  • Adenovirus E1A Proteins / metabolism*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Cell Cycle / genetics
  • Cell Cycle Proteins / physiology*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / drug effects
  • Cyclins / metabolism
  • DNA Damage
  • DNA, Neoplasm / metabolism
  • Doxorubicin / pharmacology
  • Enzyme Inhibitors / metabolism
  • Etoposide / pharmacology
  • Histone Acetyltransferases
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Retinoblastoma / metabolism
  • Transcription Factors
  • Transcriptional Activation / genetics*
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / antagonists & inhibitors*
  • Tumor Suppressor Protein p53 / drug effects
  • Tumor Suppressor Protein p53 / metabolism*
  • p300-CBP Transcription Factors


  • Adenovirus E1A Proteins
  • CDKN1A protein, human
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA, Neoplasm
  • Enzyme Inhibitors
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Etoposide
  • Doxorubicin
  • Acetyltransferases
  • Histone Acetyltransferases
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor