Considerable evidence suggests that the E2F transcription factor family play a critical role in cell growth control. Study of E2F1 protein, a major component of E2F has shown that its activation domain could be repressed by direct binding of the retinoblastoma protein and activated by binding of the proteins MDM2 and CBP to this same domain. The same region of the activation domain of E2F1 is bound by RB and CBP, which display antagonistic effect on E2F1 activity. The aim of this project will be to establish the relationship between RB and CBP interaction at the E2F1 activation domain. This will include a biochemical analysis in order to characterize the mechanism of RB and CBP binding to the E2F1 activation domain. It will also include a biological analysis, in order to establish whether CBP, through the activation of E2F1, can overcome the RB-induced G1 arrest, induce S-phase progression or display oncogenic activity in cooperation with an activated ras oncogene.