DNA-binding and trans-activation properties of Drosophila E2F and DP proteins.
The temporal activation of E2F transcriptional activity appears to be an important component of the mechanisms that prepare mammalian cells for DNA replication. Regulation of E2F activity appears to be a highly complex process, and the dissection of the E2F pathway will be greatly facilitated by the ability to use genetic approaches. We report the isolation of two Drosophila genes that can stimulate E2F-dependent transcription in Drosophila cells. One of these genes, dE2F, contains three domains that are highly conserved in the human homologs E2F-1, E2F-2, and E2F-3. Interestingly, one of these domains is highly homologous to the retinoblastoma protein (RB)-binding sequences of human E2F genes. The other gene, dDP, is closely related to the human DP-1 and DP-2 genes. We demonstrate that dDP and dE2F interact and cooperate to give sequence-specific DNA binding and optimal trans-activation. These features suggest that endogenous Drosophila E2F, like human E2F, may be composed of heterodimers and may be regulated by RB-like proteins. The isolation of these genes will provide important reagents for the genetic analysis of the E2F pathway.
Laboratory of Molecular Oncology, Massachusetts General Hospital Cancer Center, Charlestown 02129.
B D
BD
Dynlacht
A
A
Brook
M
M
Dembski
L
L
Yenush
N
N
Dyson
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002460:Cell Line; D003001:Cloning, Molecular; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050703:E2F2 Transcription Factor; D050699:E2F3 Transcription Factor; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010957:Plasmids; D056465:Retinoblastoma-Binding Protein 1; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000096:biosynthesis / Q000378:metabolism*; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*; D014162:Transfection
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C088053:Dp transcription factor, Drosophila; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D050703:E2F2 Transcription Factor; C493761:E2F2 protein, human; D050699:E2F3 Transcription Factor; C493754:E2f1 protein, mouse; D056465:Retinoblastoma-Binding Protein 1; C493735:TFDP1 protein, human; D015534:Trans-Activators; D050680:Transcription Factor DP1; D014157:Transcription Factors