ASSOCIATION OF P300 AND CBP WITH SIMIAN-VIRUS-40 LARGE T-ANTIGEN

p300 and the CREB-binding protein CBP are two large nuclear phosphopro teins that are structurally highly related. Both function, in part, as transcriptional adapters and are targeted by the adenovirus E1A oncop rotein. We show here that p300 and CBP interact with another transform ing protein, the simian virus 40 large T antigen (T). This interaction depends on the integrity of a region of T which is critical for its t ransforming and mitogenic properties and includes its LXCXE Rb-binding motif. T interferes with normal p300 and CBP function on at least two different levels. The presence of T alters the phosphorylation states of both proteins and inhibits their transcriptional activities on cer tain promoters. Although E1A and T show little sequence similarity, th ey interact with the same domain of p300 and CBP, suggesting that this region exhibits considerable flexibility in accommodating diverse pro tein ligands.