Factor-specific modulation of CREB-binding protein acetyltransferase activity

CREB-binding proteins (CBP) and p300 are essential transcriptional coactiva tors for a large number of regulated DNA-binding transcription factors, inc luding CREB, nuclear receptors, and STATs. CBP and p300 function in part by mediating the assembly of multiprotein complexes that contain additional c ofactors such as p300/CBP interacting protein (p/CIP), a member of the p160 /SRC family of coactivators, and the p300/CBP associated factor p/CAF. In a ddition to serving as molecular scaffolds, CBP and p300 each possess intrin sic acetyltransferase activities that are required for their function as co activators. Here we report that the adenovirus E1A protein inhibits the ace tyltransferase activity of CBP on binding to the C/H3 domain, whereas bindi ng of CREB, or a CREB/E1A fusion protein to the KIX domain, fails to inhibi t CBP acetyltransferase activity. Surprisingly, p/CIP can either inhibit or stimulate CBP acetyltransferase activity depending on the specific substra te evaluated and the functional domains present in the p/CIP protein. While the CBP interaction domain of p/CIP inhibits acetylation of histones H3, H 4, or high mobility group by CBP, it enhances acetylation of other substrat es, such as Pit-1. These observations suggest that the acetyltransferase ac tivities of CBP/p300 and p/CAF can be differentially modulated by factors b inding to distinct regions of CBP/p300, Because these interactions are like ly to result in differential effects on the coactivator functions of CBP/p3 00 for different classes of transcription factors, regulation of CBP/p300 a cetyltransferase activity may represent a mechanism for integration of dive rse signaling pathways.