Physical and functional interactions between p53 and cell cycle co-operating transcription factors, E2F1 and DP1.
One way in which wild-type p53 is able to regulate cell cycle progression is thought to be via the induction of its downstream target gene Waf1/CIP1, thus indirectly regulating the transcriptional activity of E2F. The E2F transcription factors are known to be key effectors of the cell cycle. We report here that there is a physical and functional interaction between p53 and two of the components of the E2F transcription factors, E2F1 and DP1. The expression of wild-type p53 can inhibit the transcriptional activity of E2F, and the expression of both E2F1 and DP1 can also downregulate p53-dependent transcription. The transcriptional activity of p53 is known to be inhibited by the direct binding of mdm2, but we demonstrate here that both E2F1 and DP1 can inhibit p53 transcriptional activity independently of mdm2. Detailed studies of protein-protein interactions have provided evidence that E2F1 and its co-operating factor DP1 can complex with p53 both in vitro and in vivo.
O'Connor
D J
DJ
Ludwig Institute for Cancer Research, St Mary's Hospital Medical School, London, UK.
Lam
E W
EW
Griffin
S
S
Zhong
S
S
Leighton
L C
LC
Burbidge
S A
SA
Lu
X
X
D000818:Animals; D002352:Carrier Proteins; D002453:Cell Cycle / Q000235:genetics* / Q000502:physiology*; D018797:Cell Cycle Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000502:physiology; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D016158:Genes, p53; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051736:Proto-Oncogene Proteins c-mdm2; D016160:Retinoblastoma Protein / Q000502:physiology; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C493754:E2f1 protein, mouse; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; C493735:TFDP1 protein, human; C493736:Tfdp1 protein, mouse; D050680:Transcription Factor DP1; D014157:Transcription Factors; C497206:MDM2 protein, human; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2