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A family of transcriptional adaptor proteins targeted by the E1A oncoprotein

Z Arany1, D Newsome, E Oldread

  • 1Dana Farber Cancer Institute, Boston, Massachusetts.

Nature
|March 2, 1995
PubMed

Insights

The adenoviral E1A oncoprotein targets p300 and CBP, which are transcriptional adaptor proteins. E1A inhibits p300

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Virology

Background:

  • p300 protein regulates cell cycle, enhancers, and differentiation.
  • CBP protein coactivates CREB transcription factor and cyclic AMP-induced promoters.
  • p300 and CBP share highly similar sequences.

Purpose of the Study:

  • To investigate the functional relationship between p300, CBP, and adenoviral E1A.
  • To determine if E1A inhibits p300 and CBP transcriptional activity.
  • To explore the in vivo interaction between E1A and CBP.

Main Methods:

  • Assessing transcriptional stimulation by p300.
  • Testing the inhibitory effect of E1A on p300 activity.
  • Investigating CBP's association with DNA-bound CREB family members.
  • Examining E1A and CBP interaction in vivo.

Main Results:

  • p300 stimulates transcription, and this activity is specifically inhibited by E1A.
  • CBP forms DNA-bound complexes with CREB family members.
  • E1A and CBP interact in vivo.
  • E1A represses cAMP-dependent transcription, indicating functional targeting of CBP.

Conclusions:

  • p300 and CBP constitute a family of transcriptional adaptor proteins.
  • Adenoviral E1A oncoprotein specifically targets this p300/CBP protein family.
  • E1A's interaction with CBP and inhibition of transcriptional activity are key mechanisms of viral oncogenesis.

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