STIMULATION OF E2F1 DP1 TRANSCRIPTIONAL ACTIVITY BY MDM2 ONCOPROTEIN/

THE MDM2 proto-oncogene is found amplified in a variety of tumours(1). The oncogenic capacity of the MDM2 protein is attributed to its abili ty to bind the p53 tumour-suppressor protein and mask its transcriptio nal activation potential(2,3). Here we show that MDM2 makes a function al contact with two cooperating transcription factors, E2F1 and DP1 (r efs 4, 5), which are involved in S-phase progression(6). MDM2 contacts the activation domain of E2F1 using residues conserved in the activat ion domain of p53. However, in contrast to its repression of p53 activ ity, MDM2 stimulates the activation capacity of E2F1/DP1. These result s indicate that MDM2 not only releases a proliferative block by silenc ing the tumour suppressor p53, it also positively augments proliferati on by stimulating the S-phase inducing transcription factors E2F1/DP1.