BINDING AND MODULATION OF P53 BY P300 CBP COACTIVATORS/

The adenovirus E1A and SV40 large-T-antigen oncoproteins bind to membe rs of the p300/CBP transcriptional coactivator family. Binding of p300 /CBP is implicated in the transforming mechanisms of EIA and T-antigen oncoproteins. A common region of the T antigen is critical for bindin g both p300/CBP and the tumour suppressor p53 (ref. 1), suggesting a l ink between the functions of p53 and p300. Here we report that p300/CB P binds to p53 in the absence of viral oncoproteins, and that p300 and p53 colocalize within the nucleus and coexist in a stable DNA-binding complex. Consistent with its ability to bind to p300, E1A disrupted f unctions mediated by p53. It reduced p53-mediated activation of the p2 1 and bax promoters, and suppressed p53-induced cell-cycle arrest and apoptosis. We conclude that members of the p300/CBP family are transcr iptional adaptors for p53, modulating its checkpoint function in the G 1 phase of the cell cycle and its induction of apoptosis. Disruption o f p300/p53-dependent growth control may be part of the mechanism by wh ich E1A induces cell transformation. These results help to explain how p53 mediates growth and checkpoint control, and how members of the p3 00/CBP family affect progression from G1 to the S phase of the cell cy cle.