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Identification and Characterization of E2F7, a Novel Mammalian E2F Family Member Capable of Blocking Cellular Proliferation
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The mammalian E2F family of transcription factors plays a crucial role in the regulation of cellular proliferation, apoptosis, and differentiation. Consistent with its biological role in a number of important cellular processes, E2F regulates the expression of genes involved in cell cycle, DNA replication, DNA repair, and mitosis. It has proven difficult, however, to determine the specific roles played by the various known family members in these cellular processes. The work presented here now extends the complexity of this family even further by the identification of a novel E2F family member, which we now term E2F7. Like the expression of the known E2F activators, E2F1, E2F2, and E2F3, the expression of E2F7 is growth-regulated, at least in part, through E2F binding elements on its promoter, and its protein product is localized to the nucleus and associates with DNA E2F recognition sites with high affinity. A number of salient features, however, make this member unique among the E2F family. First, the E2F7 gene encodes a protein that possesses two distinct DNA-binding domains and that lacks a dimerization domain as well as a transcriptional activation and a retinoblastoma-binding domain. In contrast to the E2F activators, E2F7 can block the E2F-dependent activation of a subset of E2F target genes as well as mitigate cellular proliferation of mouse embryo fibroblasts. These findings identify E2F7 as a novel member of the mammalian E2F transcription factor family that has properties of a transcriptional repressor capable of negatively influencing cellular proliferation.
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“Acting as mutually redundant transcriptional repressors, E2F7 and E2F8 inhibit the expression of many genes, including Aurka/b, Ccnb1, and Plk1, which encode proteins that act during mitotic progression (7, 8, 11).”
From Wnt signaling regulates hepatocyte cell division by a transcriptional repressor cascade (2022) · cites this paper as [11]
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Zhou, Y., Nakajima, R., Shirasawa, M., Fikriyanti, M., Zhao, L., Iwanaga, R., Bradford, A. P., Kurayoshi, K., Araki, K., & Ohtani, K. (2023) · Biology · doi:10.3390/biology12121511 · Cited by 52
Lavrrar, J. L., & Farnham, P. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402692200 · Cited by 45
Sozzani, R., Maggio, C., Giordo, R., Umana, E., Ascencio‐Ibáñez, J. T., Hanley-Bowdoin, L. K., Bergounioux, C., Cella, R., & Albani, D. (2009) · Plant Molecular Biology · doi:10.1007/s11103-009-9577-8 · Cited by 47
Gene expression in the preimplantation embryo: in-vitro developmental changes
Wang, S., Cowan, C. A., Chipperfield, H., & Powers, R. D. (2005) · Reproductive BioMedicine Online · doi:10.1016/s1472-6483(10)61668-9 · Cited by 45
E2F7 regulates transcription and maturation of multiple microRNAs to restrain cell proliferation
Mitxelena, J., Apraiz, A., Vallejo-Rodríguez, J., Malumbres, M., & Zubiaga, A. M. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw146 · Cited by 46
Wang, C., Li, S., Xu, J., Niu, W., & Li, S. (2018) · British Journal of Biomedical Science · doi:10.1080/09674845.2018.1520066 · Cited by 43
Wu, J., Sabirzhanov, B., Stoica, B. A., Lipinski, M. M., Zhao, Z., Zhao, S., Ward, N., Yang, D., & Faden, A. I. (2015) · Cell Cycle · doi:10.1080/15384101.2015.1104436 · Cited by 40
RhoBTB2 (DBC2) Is a Mitotic E2F1 Target Gene with a Novel Role in Apoptosis
Freeman, S. N., Ma, Y., & Cress, W. D. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m705986200 · Cited by 43
Comparative Analysis of E2F Family Member Oncogenic Activity
Chen, C., & Wells, A. D. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000912 · Cited by 41
Liu, B., Shats, I., Angus, S. P., Gatza, M. L., & Nevins, J. R. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.467506 · Cited by 45
dDP Is Needed for Normal Cell Proliferation
Frolov, M. V., Moon, N.-S., & Dyson, N. J. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.8.3027-3039.2005 · Cited by 39
Regulation of the Embryonic Cell Cycle During Mammalian Preimplantation Development
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E2F6 negatively regulates ultraviolet-induced apoptosis via modulation of BRCA1
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Agger, K., Santoni‐Rugiu, E., Holmberg, C., Karlström, O. H., & Helin, K. (2004) · Oncogene · doi:10.1038/sj.onc.1208248 · Cited by 43
Joshi, B., Ordonez‐Ercan, D., Dasgupta, P., & Chellappan, S. (2005) · Oncogene · doi:10.1038/sj.onc.1208206 · Cited by 39
A Conserved E2F6-Binding Element in Murine Meiosis-Specific Gene Promoters1
Kehoe, S. M., Oka, M., Hankowski, K. E., Reichert, N., García, S., McCarrey, J. R., Gaubatz, S., & Terada, N. (2008) · Biology of Reproduction · doi:10.1095/biolreprod.108.067645 · Cited by 42
Atypical E2fs Control Lymphangiogenesis through Transcriptional Regulation of Ccbe1 and Flt4
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Gene network analysis in plant development by genomic technologies
Wellmer, F., & Riechmann, J. L. (2005) · The International Journal of Developmental Biology · doi:10.1387/ijdb.051991fw · Cited by 38
E2F7 Is a Potent Inhibitor of Liver Tumor Growth in Adult Mice
Moreno, E., Toussaint, M. J. M., van Essen, S. C., Bongiovanni, L., van Liere, E. A., Koster, M. H., Yuan, R., van Deursen, J. M., Westendorp, B., & de Bruin, A. (2021) · Hepatology · doi:10.1002/hep.31259 · Cited by 37
“(3-7) They are referred to as atypical E2Fs because they possess unique structural features compared to the other E2Fs.”
Background
Metadata
- Authors
- de Bruin, A., Maiti, B., Jakoi, L., Timmers, C., Buerki, R., & Leone, G.
- Affiliations
- The Ohio State University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Leone, Gustavo
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-10
- Volume
- 278
- Issue
- 43
- Pages
- 42041-42049
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2122511750
- Cited by
- 221
- References
- 20
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 9 · 2023: 4 · 2022: 5 · 2021: 9 · 2020: 10 · 2019: 7 · 2018: 9 · 2017: 3 · 2016: 10 · 2015: 6 · 2014: 2 · 2013: 9 · 2012: 6
- FWCI
- 10.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- E2F7, E2F transcription factors, transcriptional repressor, cell proliferation, growth inhibition, DNA-binding domain, E2F target genes, mouse embryonic fibroblasts, cell cycle regulation
- MeSH terms
- Animals, Binding Sites, Cell Division, Cloning, Molecular, DNA, Embryo, Mammalian, Fibroblasts, Gene Expression Regulation, Promoter Regions, Genetic, Repressor Proteins, Transfection, Protein Structure, Tertiary, DNA, Complementary, Response Elements, Peptide Elongation Factor 2, E2F7 Transcription Factor, Mice
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