CREB-BINDING PROTEIN AND P300 CBP-ASSOCIATED FACTOR ARE TRANSCRIPTIONAL COACTIVATORS OF THE P53 TUMOR-SUPPRESSOR PROTEIN/

The structurally related transcriptional coactivators p3OO and CBP pos sess histone acetyltransferase activity and associate with P/CAF, whic h is also a histone acetyltransferase. CBP and p300 have properties of tumor suppressor proteins; their interaction with P/CAF is disrupted by the adenoviral E1A oncoprotein, and the genes encoding CBP and p300 are mutated in human cancer. We observed a physical interaction betwe en the transactivation domain of the p53 tumor suppressor protein and CBP. Furthermore, CBP and P/CAF enhanced the ability of p53 to activat e expression of the endogenous p21(cip1/waf1) gene, whereas E1A and do minant negative CBP mutants suppressed p53-dependent p21(cip1/waf1) ex pression. These studies link two tumor suppressor families and provide a framework for understanding the molecular mechanism by which p53 ac tivates transcription.