Studies on the mechanisms through which the oncogene products of DNA tumour viruses subvert the physiological processes that control cell proliferation have yielded many important insights into the mammalian cell cycle. In the case of the adenovirus E1a oncoprotein, a number of distinct protein domains are required for it to exert its growth-promoting effects. These domains allow E1a to associate physically with and inactivate cellular proteins that normally restrain proliferation. Recently, a group of E1a-interacting proteins discovered in part through studies on viral oncoproteins has become a major focus of research activity. Members of this family, known as p300/CBP, function to regulate transcription and chromatin, and thereby enable diverse signals, particularly those that facilitate differentiation, to be integrated and coordinated with gene expression. Furthermore, accumulating evidence connects genes encoding p300/CBP with diseases such as cancer.