ADENOVIRAL E1A-ASSOCIATED PROTEIN P300 AS A FUNCTIONAL HOMOLOG OF THETRANSCRIPTIONAL COACTIVATOR CBP

THE 265K nuclear protein CBP was initially identified as a coactivator for the protein kinase A (PKA)-phosphorylated form of the transcripti on factor CREB(1). The domains in CBP that are involved in CREB bindin g and transcriptional activation are highly related to the adenoviral E1A-associated cellular protein p300 (refs 2, 3), and to two hypotheti cal proteins from Caenorhabditis elegans, R10E11.1 and K03H1.10 (refs 4 and 5, respectively), whose functions are unknown. Here, we show tha t CBP and p300 have similar binding affinity for the PKA-phosphorylate d form of CREB, and that p300 can substitute for CBP in potentiating C REB-activated gene expression. We find that E1A binds to CBP through a domain conserved with p300 acid represses the CREB-dependent co-activ ator functions of both CBP and p300. Our results indicate that the gen e repression and cell immortalization functions associated with E1A in volve the inactivation of a family of related proteins that normally p articipate in second-messenger-regulated gene expression.