Direct coupling of the cell cycle and cell death machinery by E2F
Abstract
Unrestrained E2F activity forces S phase entry and promotes apoptosis through p53-dependent and -independent mechanisms. Here, we show that deregulation of E2F by adenovirus E1A, loss of Rb or enforced E2F-1 expression results in the accumulation of caspase proenzymes through a direct transcriptional mechanism. Increased caspase levels seem to potentiate cell death in the presence of p53-generated signals that trigger caspase activation. Our results demonstrate that mitogenic oncogenes engage a tumour suppressor network that functions at multiple levels to efficiently induce cell death. The data also underscore how cell cycle progression can be coupled to the apoptotic machinery.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A MAD2 genomic fragment containing the E2F sites conferred E2F responsiveness to a luciferase reporter in U-2OS cells, comparable to the caspase-7 promoter.
“a MAD2 genomic fragment containing the E2F sites (Supplementary Fig. S1) conferred E2F responsiveness to a luciferase reporter following transient transfection into IMR90 (data not shown) or U-2OS cells (Fig. 1d) in a manner comparable to the caspase-7 promoter, an established E2F target 15 .”
From Rb inactivation promotes genomic instability by uncoupling cell cycle progression from mitotic control (2004) · cites this paper as [15]
Cites
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,178 · cited 1× · see citing works
“Primary MEFs from wild type, p53 −/− , ARF −/− , Rb −/− , p53 −/− Rb −/− and p53 −/− bax −/− mice were isolated and cultured as describe”
Self-citationSibling rivalry in the E2F family
Trimarchi, J. M., & Lees, J. A. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm714 · Cited by 1,158 · see citing works
Tsai, K. Y., Hu, Y., Macleod, K. F., Crowley, D., Yamasaki, L., & Jacks, T. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80274-9 · Cited by 372 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence
Narita, M., Nuñez, S., Heard, E., Narita, M., Lin, A. W., Hearn, S. A., Spector, D. L., Hannon, G. J., & Lowe, S. W. (2003) · Cell · doi:10.1016/s0092-8674(03)00401-x · Cited by 2,278 · see citing works
Self-citationCaspases in apoptosis and beyond
Li, J., & Yuan, J. (2008) · Oncogene · doi:10.1038/onc.2008.297 · Cited by 1,090 · see citing works
Hernando, E., Nahlé, Z., Juan, G., Diaz-Rodriguez, E., Alaminos, M., Hemann, M., Michel, L., Mittal, V., Gerald, W., Benezra, R., et al. (2004) · Nature · doi:10.1038/nature02820 · Cited by 562 · see citing works
Self-citationp53 and E2f: partners in life and death
Polager, S., & Ginsberg, D. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2718 · Cited by 498 · see citing works
<i>BNIP3</i> Is an RB/E2F Target Gene Required for Hypoxia-Induced Autophagy
Tracy, K., Dibling, B. C., Spike, B. T., Knabb, J. R., Schumacker, P., & Macleod, K. F. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.02246-06 · Cited by 369 · see citing works
Coordinated regulation of life and death by RB
Chau, B. N., & Wang, J. Y. J. (2003) · Nature Reviews Cancer · doi:10.1038/nrc993 · Cited by 292 · see citing works
Cellular senescence and cancer treatment
Schmitt, C. A. (2007) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2006.08.005 · Cited by 254 · see citing works
Duxbury, M. S., Ito, H., Zinner, M. J., Ashley, S. W., & Whang, E. E. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-1183-3 · Cited by 192 · see citing works
Shamma, A., Takegami, Y., Miki, T., Kitajima, S., Noda, M., Obara, T., Okamoto, T., & Takahashi, C. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.03.001 · Cited by 140 · see citing works
Nahlé, Z., Hsieh, M., Pietka, T., Coburn, C. T., Grimaldi, P. A., Zhang, M. Q., Das, D., & Abumrad, N. A. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m706478200 · Cited by 122 · see citing works
Self-citationRB signaling prevents replication-dependent DNA double-strand breaks following genotoxic insult
Bosco, E. E. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkg919 · Cited by 97 · see citing works
Purushotham, A., Xu, Q., Lu, J., Foley, J. F., Yan, X., Kim, D.-H., Kemper, J. K., & Li, X. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.05988-11 · Cited by 87 · see citing works
Yao, K., Gietema, J. A., Shida, S., Selvakumaran, M., Fonrose, X., Haas, N. B., Testa, J., & O'Dwyer, P. J. (2005) · British Journal of Cancer · doi:10.1038/sj.bjc.6602864 · Cited by 82 · see citing works
Differential role of RB in response to UV and IR damage
Bosco, E. E. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki283 · Cited by 24 · see citing works
- Authors
- Nahle, Z., Polakoff, J., Davuluri, R. V., McCurrach, M. E., Jacobson, M. D., Narita, M., Zhang, M. Q., Lazebnik, Y., Bar-Sagi, D., & Lowe, S. W.
- Affiliations
- Cold Spring Harbor Laboratory (US)
- Stony Brook University (US)
- Corresponding author
- Lowe, Scott W.
- Venue
- Nature Cell Biology
- Published
- 2002-10-21
- Volume
- 4
- Issue
- 11
- Pages
- 859-864
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2166668167
- Cited by
- 421
- References
- 3
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 7 · 2022: 10 · 2021: 8 · 2020: 8 · 2019: 5 · 2018: 7 · 2017: 10 · 2016: 4 · 2015: 9 · 2014: 10 · 2013: 17 · 2012: 21
- FWCI
- 17.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Funders
- National Institutes of Health
- National Human Genome Research Institute (R01HG001696, HG01696)
- National Cancer Institute (CA13106, P01CA013106, P30CA008748)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- E2F transcription factors, cell cycle, apoptosis, p53, retinoblastoma protein, adenovirus E1A, E2F1, transcriptional regulation, S phase entry
- MeSH terms
- Animals, Cell Cycle, DNA-Binding Proteins, Fibroblasts, Humans, Luciferases, Models, Biological, Models, Genetic, Promoter Regions, Genetic, RNA, Time Factors, Transcription Factors, Transcription, Genetic, Blotting, Northern, Tumor Suppressor Protein p53, Retinoblastoma Protein, Apoptosis, Adenovirus E1A Proteins, Cell Cycle Proteins, CpG Islands, Caspases, Cytochromes c, Cell Line, Tumor, E2F Transcription Factors, E2F1 Transcription Factor, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
