CBP-induced stimulation of c-Fos activity is abrogated by E1A.
The CBP protein stimulates transcription of cAMP-responsive genes by binding to the phosphorylated activation domain of the CREB transcription factor. Here we show that CBP stimulates transcription of Fos/Jun activity in F9 cells and that this response of mediated, at least partly, via c-Fos. We show that CBP binds c-Fos in a phosphorylation-independent manner in vitro, using a domain distinct from that required to bind CREB. When this CBP domain is linked to the activation domain of VP16 it can stimulate GAL4-Fos activity in vivo. The domain of CBP that binds c-Fos is also used to contact the E1A protein. We therefore asked whether the documented repression of AP1 activity by E1A is due to sequestration of CBP from c-Fos. We show that E1A 12S can repress c-Fos activation functions. The use of E1A mutants indicates that binding of CBP, but not RB, to E1A is essential for E1A-mediated repression. These data support a model whereby E1A can modulate AP1 activity by directly competing for the CBP co-activator protein.
Bannister
A J
AJ
Wellcome/CRC Institute, University of Cambridge, UK.
Kouzarides
T
T
D017500:Adenovirus E1A Proteins / Q000378:metabolism* / Q000502:physiology; D000595:Amino Acid Sequence; D050882:CREB-Binding Protein; D002460:Cell Line; D017405:Herpes Simplex Virus Protein Vmw65 / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D017500:Adenovirus E1A Proteins; D017405:Herpes Simplex Virus Protein Vmw65; D009687:Nuclear Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050882:CREB-Binding Protein; C494363:CREBBP protein, human