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THE MDM2 proto-oncogene is found amplified in a variety of tumours1. The oncogenic capacity of the MDM2 protein is attributed to its ability to bind the p53 tumour-suppressor protein and mask its transcriptional activation potential2,3. Here we show that MDM2 makes a functional contact with two cooperating transcription factors, E2F1 and DPI (refs 4, 5), which are involved in S-phase progression6. MDM2 contacts the activation domain of E2F1 using residues conserved in the activation domain of p53. However, in contrast to its repression of p53 activity, MDM2 stimulates the activation capacity of E2F1/DP1. These results indicate that MDM2 not only releases a proliferative block by silencing the tumour suppressor p53, it also positively augments proliferation by stimulating the S-phase inducing transcription factors E2F1/DPI. © 1995 Nature Publishing Group.

Original publication

DOI

10.1038/375691a0

Type

Journal article

Journal

Nature

Publication Date

01/01/1995

Volume

375

Pages

691 - 694