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

Abstract

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