Autoregulatory control of E2F1 expression in response to positive and negative regulators of cell cycle progression.
Both positive and negative signals govern the progression of cells from G1 into S phase, and a variety of data implicate the E2F transcription factor as a target for the action of one class of negative regulators, the Rb family of growth suppressors. We now find that the E2F1 gene, which encodes one of the components of E2F activity, is subject to autoregulatory control during progression from G0 to S phase and that this primarily reflects a negative control in G0 and early G1, a time when the majority of E2F activity exits as a complex with Rb family members. In addition, we find that deregulated expression of G1 cyclins in quiescent cells stimulates the E2F1 promoter and that this is augmented by coexpression of cyclin-dependent kinases in an E2F-dependent manner. We conclude that the E2F1 gene is a downstream target for G1 cyclin-dependent kinase activity, most likely as a consequence of phosphorylation of Rb family members, and that the autoregulation of E2F1 transcription may provide a sensitive switch for regulating the accumulation of E2F activity during the transition from G1 to S phase.
Department of Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710.
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DG
Johnson
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Ohtani
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Nevins
D001483:Base Sequence; D002352:Carrier Proteins; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005260:Female; D016193:G1 Phase; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis; D008969:Molecular Sequence Data; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D015183:Restriction Mapping; D016160:Retinoblastoma Protein / Q000378:metabolism; D056465:Retinoblastoma-Binding Protein 1; D016196:S Phase; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection; D001616:beta-Galactosidase / Q000096:biosynthesis
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D008156:Luciferases; D018844:Cyclin-Dependent Kinases; D001616:beta-Galactosidase