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.
| Original language | English |
|---|---|
| Pages (from-to) | 1402-1406 |
| Number of pages | 5 |
| Journal | Cancer Research |
| Volume | 54 |
| Issue number | 6 |
| State | Published - Mar 15 1994 |
Keywords
- Base Sequence
- CDC2 Protein Kinase/genetics
- Carrier Proteins
- Cell Cycle Proteins
- Cell Cycle/physiology
- Cyclin D1
- Cyclins/genetics
- DNA Polymerase II/genetics
- DNA, Antisense/genetics
- DNA, Complementary/genetics
- DNA, Neoplasm/genetics
- DNA-Binding Proteins
- E2F Transcription Factors
- E2F1 Transcription Factor
- Glioblastoma/genetics
- Humans
- Molecular Sequence Data
- Oncogene Protein p55(v-myc)/genetics
- Oncogene Proteins/genetics
- Promoter Regions, Genetic/genetics
- Retinoblastoma-Binding Protein 1
- S Phase/physiology
- Transcription Factor DP1
- Transcription Factors/genetics
- Transcription, Genetic/genetics
- Transcriptional Activation/genetics
- Tumor Cells, Cultured