Abstract
Both the heterodimeric transcription factor, E2F, and the G1 cyclin, cyclin E, are required for the G1-S transition at the start of the metazoan cell cycle. It has been established that cyclin E can act as an upstream activator of E2F. In addition to this action, we show here that cyclin E has an essential role in DNA replication distinct from activating E2F. We have created transgenic Drosophila capable of inducible, ectopic production of E2F activity. Simultaneous overexpression of both Drosophila E2F subunits, dE2F and dDP, in embryos stimulated the expression of multiple E2F-target genes including cyclin E, and also caused the initiation of S phase. Mutation of cyclin E prevented the initiation of S phase after overexpression of dE2F/dDP without affecting induction of target gene expression. Thus, E2F-directed transcription cannot bypass loss of cyclin E in Drosophila embryos.
References
86
Referenced
94
10.1101/gad.10.11.1422
10.1101/gad.8.22.2680
10.1101/gad.9.11.1340
{'key': '2021111418401079000_10.19.2505.4', 'first-page': '4994', 'article-title': 'Transcription factor E2F is required for efficient expression of the hamster dihydrofolate reductase gene in vitro and in vivo.', 'volume': '9', 'year': '1989', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Transcription factor E2F is required for efficient expression of the hamster dihydrofolate reductase gene in vitro and in vivo. (1989)10.1016/0896-6273(89)90112-8
-
Campos-Ortega, J.A. and V. Hartenstein. 1985. The embryonic development of Drosophila melanogaster. Springer-Verlag, Berlin, Germany.
(
10.1007/978-3-662-02454-6
) 10.1016/0092-8674(91)90557-F
10.1002/j.1460-2075.1992.tb05231.x
/ EMBO J. / Cell cycle regulation of the human cdc2 gene. (1992)10.1128/MCB.15.8.4215
/ Mol. Cell. Biol. / Cellular targets for activation by the E2F1 transcription factor include DNA synthesis- and G1/S-regulatory genes. (1995)10.1101/gad.9.23.2873
10.1002/j.1460-2075.1995.tb00162.x
/ EMBO J. / Roles and regulation of Cln-Cdc28 kinases at the start of the cell cycle of Saccharomyces cerevisiae. (1995)10.1016/S0021-9258(17)42259-9
/ J. Biol. Chem. / G1/S-regulated E2F-containing protein complexes bind to the mouse thymidine kinase gene promoter. (1994)10.1016/0092-8674(93)90137-F
10.1101/gad.10.10.1206
10.1002/j.1460-2075.1996.tb00738.x
/ EMBO. J. / Ectopic expression of dE2F and dDP induces cell proliferation and death in the Drosophila eye. (1996)10.1126/science.1329201
10.1242/dev.120.6.1503
/ Development / Developmental control of a G1-S transcriptional program in Drosophila. (1994)10.1101/gad.9.12.1456
10.1101/gad.9.12.1445
10.1073/pnas.91.14.6359
{'key': '2021111418401079000_10.19.2505.21', 'first-page': '81', 'article-title': 'pRB, p107 and the regulation of the E2F transcription factor.', 'volume': '18', 'year': '1994', 'journal-title': 'J. Cell. Sci. Suppl.'}
/ J. Cell. Sci. Suppl. / pRB, p107 and the regulation of the E2F transcription factor. (1994)10.1016/0092-8674(90)90012-4
10.1016/0092-8674(93)90136-E
- Foe, V.E., G.M. Odell, and B.A. Edgar. 1993. Mitosis and morphogenesis in the Drosophila embryo: Point and counterpoint. In The development of Drosophila melanogaster (ed. M. Bate and A. Martinez Arias), pp. 149–300. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York.
10.1101/gad.8.22.2665
10.1038/362083a0
10.1242/jcs.108.9.2945
/ J. Cell. Sci. / Functional conservation of the cell cycle-regulating transcription factor DRTF1/E2F and its pathway of control in Drosophila melanogaster. (1995)10.1007/BF00399871
10.1016/0092-8674(94)90541-X
10.1016/0962-8924(93)90150-Y
10.1016/0092-8674(92)90107-N
10.1002/j.1460-2075.1994.tb06399.x
/ EMBO J. / Mutagen sensitivity and suppression of position-effect variegation result from mutations in mus209, the Drosophila gene encoding PCNA. (1994)10.1016/0092-8674(92)90249-C
10.1101/gad.10.7.851
10.1101/gad.8.13.1526
{'key': '2021111418401079000_10.19.2505.36', 'first-page': '7802', 'article-title': 'Cloning and characterization of E2F-2, a novel protein with the biochemical properties of transcription factor E2F.', 'volume': '13', 'year': '1993', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Cloning and characterization of E2F-2, a novel protein with the biochemical properties of transcription factor E2F. (1993)10.1083/jcb.130.4.755
10.1038/365349a0
10.1101/gad.8.13.1514
10.1016/0092-8674(92)90108-O
10.1101/gad.7.3.331
10.1016/0092-8674(94)90239-9
10.1126/science.1388288
10.1016/0968-0004(94)90202-X
10.1002/j.1460-2075.1993.tb05932.x
/ EMBO J. / An E2F-binding site mediates cell-cycle regulated repression of mouse B-myb transcription. (1993)10.1128/MCB.13.12.7813
10.1016/0092-8674(90)90535-M
{'key': '2021111418401079000_10.19.2505.48', 'first-page': '1054', 'article-title': 'The HIP1 binding site is required for growth regulation of the dihydrofolate reductase gene promoter.', 'volume': '12', 'year': '1992', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / The HIP1 binding site is required for growth regulation of the dihydrofolate reductase gene promoter. (1992){'key': '2021111418401079000_10.19.2505.49', 'first-page': '6607', 'article-title': 'Transcription of the E2F-1 gene is rendered cell cycle dependent by E2F DNA-binding sites within its promoter.', 'volume': '14', 'year': '1994', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Transcription of the E2F-1 gene is rendered cell cycle dependent by E2F DNA-binding sites within its promoter. (1994)10.1126/science.1411535
{'key': '2021111418401079000_10.19.2505.51', 'first-page': '1603', 'article-title': 'Functional properties of a Drosophila homolog of the E2F1 gene.', 'volume': '14', 'year': '1994', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Functional properties of a Drosophila homolog of the E2F1 gene. (1994)10.1126/science.8384376
10.1128/MCB.15.5.2612
/ Mol. Cell. Biol. / Human cyclin E, a nuclear protein essential for the G1-to-S phase transition. (1995)10.1083/jcb.121.1.101
10.1126/science.2683075
{'key': '2021111418401079000_10.19.2505.56', 'first-page': '2081', 'article-title': 'Human DNA polymerase alpha gene: Sequences controlling expression in cycling and serum-stimulated cells.', 'volume': '11', 'year': '1991', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Human DNA polymerase alpha gene: Sequences controlling expression in cycling and serum-stimulated cells. (1991)10.1073/pnas.91.23.10918
10.1128/MCB.15.7.3463
/ Mol. Cell. Biol. / Different roles for cyclins D1 and E in regulation of the G1-to-S transition. (1995)10.1128/MCB.14.3.1669
10.1242/dev.119.3.673
/ Development / A Drosophila G1-specific cyclin E homolog exhibits different modes of expression during embryogenesis. (1993)10.1242/dev.121.10.3371
/ Development / Ectopic cyclin E expression induces premature entry into S phase and disrupts pattern formation in the Drosophila eye imaginal disc. (1995)10.1073/pnas.92.6.2403
10.1101/gad.9.11.1327
10.1016/0012-1606(87)90436-2
10.1016/0092-8674(94)90193-7
{'key': '2021111418401079000_10.19.2505.66', 'first-page': '8166', 'article-title': 'Deregulated expression of E2F-1 induces S-phase entry and leads to apoptosis.', 'volume': '14', 'year': '1994', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Deregulated expression of E2F-1 induces S-phase entry and leads to apoptosis. (1994){'key': '2021111418401079000_10.19.2505.67', 'first-page': '5620', 'article-title': 'Molecular cloning of cellular genes encoding retinoblastoma-associated proteins: Identification of a gene with properties of the transcription factor E2F.', 'volume': '12', 'year': '1992', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Molecular cloning of cellular genes encoding retinoblastoma-associated proteins: Identification of a gene with properties of the transcription factor E2F. (1992)10.1016/0092-8674(93)90636-5
/ Cell / Mammalian G1 cyclins. (1993)10.1016/0092-8674(94)90540-1
10.1101/gad.9.10.1149
{'key': '2021111418401079000_10.19.2505.71', 'first-page': '1610', 'article-title': 'A protein synthesis-dependent increase in E2F1 mRNA correlates with growth regulation of the dihydrofolate reductase promoter.', 'volume': '13', 'year': '1993', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / A protein synthesis-dependent increase in E2F1 mRNA correlates with growth regulation of the dihydrofolate reductase promoter. (1993)10.1242/dev.112.4.997
/ Development / The regulation of the cell cycle during Drosophila embryogenesis: The transition to polyteny. (1991)10.1093/genetics/135.3.817
/ Genetics / Identification of genomic regions required for DNA replication during Drosophila embryogenesis. (1993)10.1128/MCB.15.1.338
/ Mol. Cell. Biol. / The Rb-related pl07 protein can suppress E2F function independently of binding to cyclin A/cdk2. (1995)10.1101/gad.9.22.2780
10.1007/BF00291041
{'key': '2021111418401079000_10.19.2505.77', 'first-page': '1593', 'article-title': 'The cdk2 kinase is required for the G1-to-S transition in mammalian cells.', 'volume': '8', 'year': '1993', 'journal-title': 'Oncogene'}
/ Oncogene / The cdk2 kinase is required for the G1-to-S transition in mammalian cells. (1993)10.1002/j.1460-2075.1992.tb05229.x
/ EMBO J. / The Cln3-Cdc28 kinase complex of S. cerevisiae is regulated by proteolysis and phosphorylation. (1992)10.1101/gad.9.7.869
10.1126/science.8266103
10.1016/0092-8674(95)90385-2
{'key': '2021111418401079000_10.19.2505.82', 'first-page': '995', 'article-title': 'Inducible acceleration of G1 progression through tetracycline-regulated expression of human cyclin E.', 'volume': '9', 'year': '1994', 'journal-title': 'Oncogene'}
/ Oncogene / Inducible acceleration of G1 progression through tetracycline-regulated expression of human cyclin E. (1994)10.1128/MCB.15.5.2536
/ Mol. Cell. Biol. / In vivo association of E2F and DP family proteins. (1995){'key': '2021111418401079000_10.19.2505.84', 'first-page': '872', 'article-title': 'Drosophila proliferating cell nuclear antigen (cyclin) gene: Structure, expression during development, and specific binding of homeodomain proteins to its 5′-flanking region.', 'volume': '10', 'year': '1990', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Drosophila proliferating cell nuclear antigen (cyclin) gene: Structure, expression during development, and specific binding of homeodomain proteins to its 5′-flanking region. (1990)10.1074/jbc.270.42.25159
10.1101/gad.7.7a.1111
Dates
Type | When |
---|---|
Created | 18 years, 2 months ago (June 5, 2007, 5:15 p.m.) |
Deposited | 3 years, 9 months ago (Nov. 14, 2021, 9:53 p.m.) |
Indexed | 2 months, 2 weeks ago (June 11, 2025, 5:29 a.m.) |
Issued | 28 years, 10 months ago (Oct. 1, 1996) |
Published | 28 years, 10 months ago (Oct. 1, 1996) |
Published Online | 28 years, 10 months ago (Oct. 1, 1996) |
Published Print | 28 years, 10 months ago (Oct. 1, 1996) |
@article{Duronio_1996, title={E2F-induced S phase requires cyclin E.}, volume={10}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.10.19.2505}, DOI={10.1101/gad.10.19.2505}, number={19}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Duronio, R J and Brook, A and Dyson, N and O’Farrell, P H}, year={1996}, month=oct, pages={2505–2513} }