The APC/C and CBP/p300 co-operate to regulate, transcription, transformation and progression through mitosis

The anaphase- promoting complex/ cyclosome ( APC/ C) is a multicomponent E3 ubiquitin ligase that, by targeting protein substrates for 26S proteasome- mediated degradation through ubiquitination, coordinates the temporal progression of eukaryotic cells through mitosis and the subsequent G1 phase of the cell cycle(1-4). Other functions of the APC/ C are, however, less well defined. Here we show that two APC/ C components, APC5 and APC7, interact directly with the coactivators CBP and p300 through protein - protein interaction domains that are evolutionarily conserved in adenovirus E1A(5-8). This interaction stimulates intrinsic CBP/ p300 acetyltransferase activity and potentiates CBP/ p300- dependent transcription. We also show that APC5 and APC7 suppress E1A- mediated transformation in a CBP/ p300- dependent manner, indicating that these components of the APC/ C may be targeted during cellular transformation. Furthermore, we establish that CBP is required in APC/ C function; specifically, gene ablation of CBP by RNA- mediated interference markedly reduces the E3 ubiquitin ligase activity of the APC/ C and the progression of cells through mitosis. Taken together, our results define discrete roles for the APC/ C - CBP/ p300 complexes in growth regulation.