Molecular characterization of Xenopus laevis DP proteins.
It is widely believed that in mammalian cells the cellular transcription factor (DRTF1/E2F integrates cell-cycle events with the transcription apparatus by interacting with important regulators of the cell cycle, such as the retinoblastoma gene product (pRb) and related proteins, cyclins, and cyclin-dependent kinases. Here, we have defined DRTF1/E2F in Xenopus laevis that, like its mammalian counterpart, specifically binds to the E2F site, is regulated during development, and interacts with pRb and related proteins. We have isolated cDNAs that encode the functional homologue of mammalian DP-1, X1 DP-1, together with a close relative, X1 DP-2. X1 DP-1, which is highly conserved with murine DP-1, is a major DNA binding component of X1 DRTF1/E2F. Both DP-1 and DP-2 synergistically interact with members of the E2F family of proteins, E2F-1, E2F-2, and E2F-3, to generate DNA binding complexes that specifically recognize the E2F site and functionally interact with E2F-1 in E2F site-dependent transcriptional activation of cellular genes. DP-1 and DP-2 encode maternally stored transcripts that are expressed during early development. In the adult however, the expression of DP-1 and DP-2 is tissue restricted. This study therefore defines a new family of transcription factors, the DP proteins, members of which can interact combinatorially with E2F proteins to generate an array of DNA binding complexes that integrate cell-cycle progression with the transcription apparatus through the E2F binding site. The tissue-specific expression of DP family members suggests that the combination of DP/E2F heterodimers that constitute DRTF1/E2F is influenced by the phenotype of the cell.
Girling
R
R
Laboratory of Eukaryotic Molecular Genetics, Medical Research Council National Institute for Medical Research, London, United Kingdom.
Bandara
L R
LR
Ormondroyd
E
E
Lam
E W
EW
Kotecha
S
S
Mohun
T
T
La Thangue
N B
NB
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050699:E2F3 Transcription Factor; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D056465:Retinoblastoma-Binding Protein 1; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014018:Tissue Distribution; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C088053:Dp transcription factor, Drosophila; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050699:E2F3 Transcription Factor; C493754:E2f1 protein, mouse; D056465:Retinoblastoma-Binding Protein 1; C493737:TFDP1 protein, Xenopus; D015534:Trans-Activators; D050680:Transcription Factor DP1; D014157:Transcription Factors; D029867:Xenopus Proteins