E2F-4, a new member of the E2F gene family, has oncogenic activity and associates with p107 in vivo.
The E2F family of transcription factors controls the expression of genes that are involved in cell cycle regulation. E2F DNA-binding activity is found in complex with the retinoblastoma protein, pRb, and with the pRb-related p107 and p130. To date, cDNAs for three members of the E2F gene family have been isolated. However, all three E2Fs associate in vivo exclusively with pRb. We report here the cloning and functional analysis of a fourth E2F family member. E2F-4 encodes a 413-amino-acid protein with significant homology to E2F-1. E2F-4 antibodies recognize a 60-kD protein in anti-p107 immunoprecipitates, indicating that E2F-4 associates with p107 in vivo. Like the other E2Fs, E2F-4 requires DP-1 for efficient DNA binding and transcriptional activation of E2F site-containing promoters. Increased expression of E2F-4 and DP-1 in SaoS-2 osteosarcoma cells causes a shift from G1-phase cells to S and G2/M-phase cells, suggesting a role for E2F-4 in regulation of cell-cycle progression. We show that expression of E2F-4 and DP-1 together with an activated ras oncogene in rat embryo fibroblasts, causes transformation, indicating that E2F-4 has oncogenic activity.
Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Amsterdam.
R L
RL
Beijersbergen
R M
RM
Kerkhoven
L
L
Zhu
L
L
Carlée
P M
PM
Voorhoeve
R
R
Bernards
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins; D005786:Gene Expression Regulation; D011905:Genes, ras; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D050720:Retinoblastoma-Like Protein p107; D015534:Trans-Activators / Q000378:metabolism; D050680:Transcription Factor DP1
D004268:DNA-Binding Proteins; C088053:Dp transcription factor, Drosophila; D029721:Drosophila Proteins; D009687:Nuclear Proteins; C489485:Rbl1 protein, mouse; D050720:Retinoblastoma-Like Protein p107; C493735:TFDP1 protein, human; D015534:Trans-Activators; D050680:Transcription Factor DP1