The E6 protein of human papillomavirus type 16 binds to and inhibits co-activation by CBP and p300

The co-activators CBP and p300 are important for normal cell differentiatio n and cell cycle progression and are the targets for viral proteins that dy sregulate these cellular processes. We show here that the E6 protein from t he oncogenic human papillomavirus type 16 (HPV-16) binds to three regions ( C/H1, C/H3 and the C-terminus) of both CBP and p300, The interaction of E6 with CBP/p300 was direct and independent of proteins known to bind the co-a ctivators, such as p53. The E6 protein from low-risk HPV type 6 did not int eract with C/H3 or the C-terminus but associated with the C/H1 domain at 50 % of the level of HPV-16. HPV-16 E6 inhibited the intrinsic transcriptional activity of CBP/p300 and decreased the ability of p300 to activate p53- an d NF-kappa B-responsive promoter elements. Interestingly, some mutations in HPV-16 E6 abrogated C/H3-E6 interactions, but did not alter the ability of E6 to associate with the C/H1 domain, suggesting that these modified prote ins could be used to delineate the functional significance of the C/H1 and C/H3 domains of CBP/p300.