Abstract
The mammalian nuclear protein E2F-1 has recently been cloned based on its ability to bind the retinoblastoma protein. To determine whether E2F-1 plays a role in the control of the cell proliferation, we introduced an inducible construct expressing an E2F-1 antisense RNA into the human glioblastoma T98G cell line and assessed DNA synthesis during the cell cycle. Expression of the antisense transcripts during the G1-S transition resulted in a marked delay in the completion of DNA synthesis. Band-shift analysis of bacterially produced E2F-1 showed that this protein bound to the promoters of human DNA polymerase-alpha, cyclin D1, and c-myb but not to the cdc2 gene promoter. E2F-1 also transactivated the bound promoters in transient transfection assays. These results suggest a major role for E2F-1 in the control of cell cycle progression via transcriptional regulation of proliferation-associated genes.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Base Sequence
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CDC2 Protein Kinase / genetics
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CDC2 Protein Kinase / metabolism
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Carrier Proteins*
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Cell Cycle / physiology
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Cell Cycle Proteins*
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Cyclin D1
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Cyclins / genetics
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Cyclins / metabolism
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DNA Polymerase II / genetics
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DNA Polymerase II / metabolism
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DNA, Antisense / genetics
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DNA, Complementary / genetics
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DNA, Neoplasm / genetics
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DNA-Binding Proteins*
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E2F Transcription Factors
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E2F1 Transcription Factor
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Glioblastoma / genetics
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Humans
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Molecular Sequence Data
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Oncogene Protein p55(v-myc) / genetics
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Oncogene Protein p55(v-myc) / metabolism
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Oncogene Proteins / genetics
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Oncogene Proteins / metabolism
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Promoter Regions, Genetic / genetics*
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Promoter Regions, Genetic / physiology
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Retinoblastoma-Binding Protein 1
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S Phase / physiology*
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Transcription Factor DP1
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription Factors / physiology*
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Transcription, Genetic / genetics*
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Transcription, Genetic / physiology
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Transcriptional Activation / genetics*
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Tumor Cells, Cultured
Substances
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Carrier Proteins
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Cell Cycle Proteins
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Cyclins
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DNA, Antisense
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DNA, Complementary
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DNA, Neoplasm
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DNA-Binding Proteins
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E2F Transcription Factors
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E2F1 Transcription Factor
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E2F1 protein, human
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Oncogene Protein p55(v-myc)
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Oncogene Proteins
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Retinoblastoma-Binding Protein 1
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Transcription Factor DP1
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Transcription Factors
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Cyclin D1
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CDC2 Protein Kinase
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DNA Polymerase II