Expression of transcription factor E2F1 induces quiescent cells to enter S phase.
Several lines of evidence implicate the E2F transcription factor as an important component of cell proliferation control. First, E2F binding sites are found in the promoters of genes responsive to proliferation signals and the level of E2F binding activity increases at a time when many of these genes are activated. Second, the tumour suppressor protein Rb, as well as the related p107 protein, complexes with E2F, resulting in an inhibition of E2F transcriptional activity. Third, oncogenic products of the DNA tumour viruses can dissociate these E2F complexes. We provide here direct evidence that E2F is involved in cellular proliferation control. Specifically, we demonstrate that overexpression of the E2F1 complementary DNA can activate DNA synthesis in cells that would otherwise growth-arrest, with an efficiency that is similar to that achieved by the expression of the adenovirus E1A gene. Moreover, microinjection of the E2F1 cDNA into quiescent cells can induce S-phase entry, whereas two E2F1 mutants, which are unable to transactivate the DHFR and TK promoters, are unable to induce S phase. We conclude that the E2F transcription factor plays an important role in progression into S phase and that this probably coincides with its capacity to stimulate transcription.
Johnson
D G
DG
Section of Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710.
Schwarz
J K
JK
Cress
W D
WD
Nevins
J R
JR
D000256:Adenoviridae / Q000235:genetics; D001973:Bromodeoxyuridine; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002460:Cell Line; D004247:DNA; D004261:DNA Replication; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D008845:Microinjections; D016160:Retinoblastoma Protein / Q000494:pharmacology; D056465:Retinoblastoma-Binding Protein 1; D016196:S Phase / Q000502:physiology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D001616:beta-Galactosidase
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D014157:Transcription Factors; D004247:DNA; D001616:beta-Galactosidase; D001973:Bromodeoxyuridine