Tumor Growth Suppression by the Coactivator p300

The p300 and closely related CREB-binding protein (CBP) acetyltransferases function as global transcriptional coactivators and play important roles in a broad spectrum of biological processes, including cell proliferation, differentiation, and apoptosis. The role of p300/CBP in tumor suppression has been proposed based on the fact that these coactivators are targeted by viral oncoproteins, and that mutations of p300/CBP associated with inactivation of the second allele have been identified in certain types of carcinoma. However, the mechanisms by which the inactivation of p300/CBP contributes to carcinogenesis have not been fully elucidated. In this review, we focus on the understanding of p300 function in tumor suppression, particularly with regard to its relationship with the TGF-β-dependent transcriptional response, which is important for the negative growth regulation of epithelial cells, and also discuss the effects of p300 mutation on the p53 pathway and cell proliferation.