Regulation of Lef-mediated transcription and p53-dependent pathway by associating beta-catenin with CBP/p300

CBP and its homologue p300 play significant roles in cell differentiation, cell cycle, and anti-oncogenesis, We demonstrated that beta -catenin, recen tly known as a potent oncogene; and CBP/p300 are associated through its CH3 region, which is a primary target of adenoviral oncoprotein E1A and variou s nuclear proteins, such as p53, cyclin E, and AP-1, and both are colocaliz ed in the nuclear :bodies. CBP/p300 potentiated Lef-mediated transactivatio n of beta -catenin, and E1A, a potent inhibitor of CBP/p300, repressed its transactivation. Furthermore, overexpression of stable beta -catenin mutant competitively suppressed the p53-dependent pathway. These may be a key mec hanism of beta -catenin involved in oncogenic events underlying disruption of tumor suppressor function through CBP/p300.