Differences in the interactions of oncogenic adenovirus 12 early region 1Aand nononcogenic adenovirus 2 early region 1A with the cellular coactivators p300 and CBP

Association with the cellular coactivators p300 and CBP Is required for the growth-regulatory function of adenoviral (Ad) early region 1A (EIA) protei ns. E1A regions necessary for these interactions overlap with domains invol ved in the induction of tumours in immunocompetent rodents through highly o ncogenic Ad12. Differences in the association of cellular factors with the respective E1A domains of Ad12 and nononcogenic Ad2 might therefore be invo lved in serotype-specific oncogenicity. We analyzed the interaction of the Ad12 E1A 235R protein with p300 and CBP. Here we demonstrate that in the ca se of Ad12, but not Ad2/5, amino acids (aa) 1-29 of E1A proteins are suffic ient to bind the p300-C/H3 domain in vivo and wild-type p300 in vitro. The conserved arginine-2,which is essential for the interaction between Ad2 E1A and p300, Was dispensable for the Ad12 E1A 235R-p300 interaction in vitro. In addition to the p300-C/H3 region, we identified a second domain within p300 (aa 1999-2200) binding to the 235R protein. Contrary to p300, the amin o-terminus and CRI are necessary to associate with Cap The aa 1-29 of the 2 35R protein but not CRI are essential for the repression of colTRE-driven g ene expression. This repression function is strictly dependent on p300 but not on CBP. (C) 1999 Academic Press.