The expression of tumor suppressor p73 is regulated at mRNA and protein levels. It has been shown that E2F1 acts as a transcriptional activator for p73. In this study, we have found that deregulated expression of E2F1 increases the mRNA level of p73, however, E2F1 promotes the degradation of p73. Immunoprecipitation experiments demonstrated that E2F1 forms a complex with p73 and inhibits the transcriptional activity of p73. Enforced expression of E2F1 induces degradation of p73 in a proteasome-independent manner. Additionally, the deletion analysis showed that E2F1(1-117) has an undetectable effect on p73, whereas E2F1(1-285) and E2F1(1-414) have an ability to promote degradation of p73 and inhibition of p73 transcriptional activity, Suggesting that the region of F2F1 between amino acid residues 118 and 285 has a critical role in the regulation of p73. Taken together, our present study indicates that E2F1 has a dual role in the regulation of p73. (C) 2009 Elsevier Inc. All rights reserved.