CBP-induced stimulation of c-Fos activity is abrogated by E1A.

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Abstract
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.