Factor-specific modulation of CREB-binding protein acetyltransferase activity

摘要

CREB-binding proteins (CBP) and p300 are essential transcriptional coactivators for a large number or regulated DNA-binding transcription factors, including CREB, nuclear receptors, and STATs. CBP and p300 function in part by mediating the assembly of multiprotein complexes that contain additional cofactors such as P300/CBP interacting protein (P/CIP), a member of the P160/SRC family of coactivators, and the P300/CBP associated factor P/CAN. In addition to serving as molecular scaffolds, CBP and p300 each possess intrinsic acetyltransferase activities that are required for their function as coactivators. Here we report that the adenovirus EIA protein inhibits the acctyltransferase activity of CBP on binding to the C/H3 domain, whereas binding of CREB, or a CREB/EIA fusion Protein to the KIX domain, fails to inhibit CBP acctyltransferase activity. Surprisingly, P/CIP can either inhibit or stimulate CBP acetyltransferase activity depending on the specific substrate evaluated and the functional domains present in the P/CIP protein. Whilc the CBP interaction domain of P/CIP inhibits acetylation of histones H3, H4, or high mobility group by CBP, it enhances acetylation of other substrates, such as Pit.l. These observations suggest that the acetyltransferase activitics of CBP/p300 and P/CAF can be differentially modulated by factors binding to distinct regions of CBP/p300. Because these interactions are likely to result in differential effects on the coactivator functions of CBP/p300 for different classes of transcription factors, regulation of CBP/p300 acetyltransferase activity