Distinct roles for Sp1 and E2F sites in the growth/cell cycle regulation of the DHFR promoter
| Autor: | D E, Jensen, A R, Black, A G, Swick, J C, Azizkhan |
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| Rok vydání: | 1997 |
| Předmět: |
Binding Sites
Transcription Genetic Sp1 Transcription Factor Recombinant Fusion Proteins Cell Cycle Cell Cycle Proteins 3T3 Cells E2F Transcription Factors DNA-Binding Proteins Mice Tetrahydrofolate Dehydrogenase Blood Cricetinae Animals Carrier Proteins Promoter Regions Genetic Transcription Factor DP1 Cell Division Retinoblastoma-Binding Protein 1 Transcription Factors |
| Zdroj: | Journal of cellular biochemistry. 67(1) |
| ISSN: | 0730-2312 |
| Popis: | Dihydrofolate reductase activity is required for many biosynthetic pathways including nucleotide synthesis. Its expression is therefore central to cellular growth, and it has become a key target for cancer chemotherapy. Transcription of the dihydrofolate reductase gene is regulated with growth, being expressed maximally in late G1/early S phase following serum stimulation of quiescent cells. This regulation is directed by a promoter which contains binding sites for only the transcription factors Sp1 and E2F. In this study, the role of these promoter elements in growth/cell cycle regulation of dihydrofolate transcription was addressed directly by transient transfection of Balb/c 3T3 cells with mutant promoter-reporter gene constructs. The E2F sites were found to repress transcription in G0 and early G1 but did not contribute to the level of transcription in late G1/S phase. In contrast, Sp1 sites were able to mediate induction of transcription from the dihydrofolate reductase promoter, as well as a heterologous promoter, following serum stimulation of quiescent cells. These findings add dihydrofolate reductase to a growing list of genes at which E2F sites are primarily repressive elements and delineate a role for Sp1 sites in the growth/cell cycle regulation of transcription. |
| Databáze: | OpenAIRE |
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