By dimerizing with E2F proteins, TFDP has profound influence on cellular E2F activities. While TFDPI and 2 enhance the DNA binding and the transcriptional activity of E2F, the newly identified member of the DP family, TFDP3 primarily functions as a negative regulator. To further characterize the inhibitory property of TFDP3, the present study specifically examined the modulatory role of TFDP3 on E2F1-induced cell death. HEK-293 cells underwent apoptosis following ectopic expression of E2F1. This effect was virtually abolished by co-transfection with TFDP3. In the meantime, the accumulation of p53 proteins and the increased expression of the proapoptotic molecules, including Bax, Puma, Noxa, and Bid were found to be suppressed. These data suggest a new mechanism for the regulation of E2F1-induced apoptosis and provide further evidence for the general involvement of TFDP3 in the regulation of E2F functions. (c) 2007 Elsevier Inc. All rights reserved.