E2F1 regulates autophagy and the transcription of autophagy genes
Abstract
The retinoblastoma pathway is often inactivated in human tumors resulting in deregulated E2F activity that can induce both proliferation and cell death. Although the role of E2F in apoptosis is well characterized, little is known regarding its putative participation in other cell death pathways. We show here that activation of E2F1 upregulates the expression of four autophagy genes-microtubule-associated protein-1 light chain-3 (LC3), autophagy-related gene-1 (ATG1), ATG5 and damage-regulated autophagy modulator (DRAM). E2F1-mediated induction of LC3, ATG1 and DRAM is direct and indeed, endogenous E2F1 can be found bound to regions encompassing the promoters of these genes. Regulation of ATG5 by E2F1 is indirect. Importantly, we demonstrate that E2F1 activation enhances autophagy and conversely, reducing endogenous E2F1 expression inhibits DNA damage-induced autophagy. These studies identify E2F1 as a transcriptional regulator of autophagy, and for the first time establish a role for E2F1 in DNA damage-induced autophagy.
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?
Functional RB may prevent autophagy in response to hypoxia through inhibition of E2F target genes.
“Recent work has demonstrated that the presence of functional RB might prevent autophagy in response to hypoxia through its inhibition of E2F target genes97,98.”
From Cellular mechanisms of tumour suppression by the retinoblastoma gene (2008) · cites this paper as [98]
Cites
LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y., & Yoshimori, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5720 · Cited by 6,605 · see citing works
Sherr, C. J. (1996) · Science · doi:10.1126/science.274.5293.1672 · Cited by 5,379 · see citing works
Autophagy as a regulated pathway of cellular degradation.
Klionsky, D., & Emr, S. (2000) · Science · doi:10.1126/science.290.5497.1717 · Cited by 3,794 · see citing works
DRAM, a p53-Induced Modulator of Autophagy, Is Critical for Apoptosis
Crighton, D., Wilkinson, S., O'Prey, J., Syed, N., Smith, P., Harrison, P. R., Gasco, M., Garrone, O., Crook, T., & Ryan, K. M. (2006) · Cell · doi:10.1016/j.cell.2006.05.034 · Cited by 1,380 · see citing works
Death by design: apoptosis, necrosis and autophagy
Edinger, A. L., & Thompson, C. B. (2004) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2004.09.011 · Cited by 1,364 · see citing works
Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes
Shimizu, S., Kanaseki, T., Mizushima, N., Mizuta, T., Arakawa-Kobayashi, S., Thompson, C. B., & Tsujimoto, Y. (2004) · Nature Cell Biology · doi:10.1038/ncb1192 · Cited by 1,358 · see citing works
The coordinate regulation of the p53 and mTOR pathways in cells
Feng, Z., Zhang, H., Levine, A. J., & Jin, S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502857102 · Cited by 1,235 · see citing works
Autophagy: dual roles in life and death?
Baehrecke, E. H. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1666 · Cited by 986 · see citing works
Formation Process of Autophagosome Is Traced with Apg8/Aut7p in Yeast
Kirisako, T., Baba, M., Ishihara, N., Miyazawa, K., Ohsumi, M., Yoshimori, T., Noda, T., & Ohsumi, Y. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.147.2.435 · Cited by 881 · see citing works
p53 and E2F-1 cooperate to mediate apoptosis.
Wu, X., & Levine, A. J. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.9.3602 · Cited by 836 · see citing works
The E2F transcriptional network: old acquaintances with new faces
Dimova, D. K., & Dyson, N. J. (2005) · Oncogene · doi:10.1038/sj.onc.1208612 · Cited by 715 · see citing works
Distinct and Overlapping Roles for E2F Family Members in Transcription, Proliferation and Apoptosis
DeGregori, J. V., & Johnson, D. G. (2006) · Current Molecular Medicine · doi:10.2174/1566524010606070739 · Cited by 499 · see citing works
Gözüaçık, D., & Kimchi, A. (2007) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(06)78006-1 · Cited by 442 · see citing works
Use of Chromatin Immunoprecipitation To Clone Novel E2F Target Promoters
Weinmann, A. S., Bartley, S. M., Zhang, T., Zhang, M. Q., & Farnham, P. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.20.6820-6832.2001 · Cited by 384 · 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
CDC25A Phosphatase Is a Target of E2F and Is Required for Efficient E2F-Induced S Phase
Vigo, E., Müller, H., Prosperini, E., Hateboer, G., Cartwright, P., Moroni, M. C., & Helin, K. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.9.6379 · Cited by 326 · see citing works
Up-regulation of Bcl-2 Homology 3 (BH3)-only Proteins by E2F1 Mediates Apoptosis
Hershko, T., & Ginsberg, D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312866200 · Cited by 322 · see citing works
Self-citationA Short Mitochondrial Form of p19ARF Induces Autophagy and Caspase-Independent Cell Death
Reef, S., Zalckvar, E., Shifman, O., Bialik, S., Sabanay, H., Oren, M., & Kimchi, A. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.04.014 · Cited by 226 · see citing works
Ginsberg, D. (2002) · FEBS Letters · doi:10.1016/s0014-5793(02)03270-2 · Cited by 186 · see citing works
Self-citationThe emerging role of E2F-1 in the DNA damage response and checkpoint control
Stevens, C., & Thangue, N. B. L. (2004) · DNA repair · doi:10.1016/j.dnarep.2004.03.034 · Cited by 136 · see citing works
p73 regulates DRAM-independent autophagy that does not contribute to programmed cell death
Crighton, D., O’Prey, J., Bell, H. S., & Ryan, K. M. (2007) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402108 · Cited by 101 · see citing works
The Proapoptotic Gene SIVA Is a Direct Transcriptional Target for the Tumor Suppressors p53 and E2F1
Fortin, A., MacLaurin, J. G., Arbour, N., Cregan, S. P., Kushwaha, N., Callaghan, S. M., Park, D. S., Albert, P. R., & Slack, R. S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m400376200 · Cited by 84 · see citing works
c-myc Induces Autophagy in Rat 3Y1 Fibroblast Cells
Tsuneoka, M., Umata, T., Kimurâ, H., Koda, Y., Nakajima, M., Kosai, K.-I., Takahashi, T., Takahashi, Y., & Yamamoto, A. (2003) · Cell Structure and Function · doi:10.1247/csf.28.195 · Cited by 42 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Autophagy · doi:10.1080/15548627.2015.1100356 · Cited by 5,894 · see citing works
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,622 · see citing works
Autophagy in malignant transformation and cancer progression
Galluzzi, L., Pietrocola, F., Bravo‐San Pedro, J. M., Amaravadi, R. K., Baehrecke, E. H., Cecconi, F., Codogno, P., Debnath, J., Gewirtz, D. A., Karantza, V., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201490784 · Cited by 1,182 · see citing works
Cellular mechanisms of tumour suppression by the retinoblastoma gene
Burkhart, D. L., & Sage, J. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2399 · Cited by 974 · see citing works
Frailty and sarcopenia: The potential role of an aged immune system
Wilson, D., Jackson, T., Sapey, E., & Lord, J. M. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.01.006 · Cited by 573 · see citing works
Atg8: an autophagy-related ubiquitin-like protein family.
Shpilka, T., Weidberg, H., Pietrokovski, S., & Elazar, Z. (2011) · Genome biology · doi:10.1186/gb-2011-12-7-226 · Cited by 543 · see citing works
“Although the transcriptional regulation of Atg8 genes is largely unknown, several reports have shown that the transcription factors FoxO1, FoxO3 and E2F1 regulate Atg8s in this process in mammalian cells [31-34].”
Backgroundp53 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
Self-citationAutophagy mediates pharmacological lifespan extension by spermidineand resveratrol
Morselli, E., Galluzzi, L., Kepp, O., Criollo, A., Maiuri, M. C., Tavernarakis, N., Madeo, F., & Kroemer, G. (2009) · Aging · doi:10.18632/aging.100110 · Cited by 213 · see citing works
The AMPK-PPARGC1A pathway is required for antimicrobial host defense through activation of autophagy
Yang, C.-S., Kim, J.-J., Lee, H.-M., Jin, H. S., Lee, S.-H., Park, J.-H., Kim, S. J., Kim, J.-M., Han, Y.-M., Lee, M.-S., et al. (2014) · Autophagy · doi:10.4161/auto.28072 · Cited by 131 · see citing works
Transcription factors and cognate signalling cascades in the regulation of autophagy
Chandra, V., Bhagyaraj, E., Parkesh, R., & Gupta, P. (2016) · Biological Reviews · doi:10.1111/brv.12177 · Cited by 26 · see citing works
Long-Term PGC1β Overexpression Leads to Apoptosis, Autophagy and Muscle Wasting
Sopariwala, D. H., Yadav, V., Badin, P.-M., Likhite, N., Sheth, M., Lorca, S., Vila, I. K., Kim, E. R., Tong, Q., Song, M. S., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-10238-9 · Cited by 14 · see citing works
- Authors
- Polager, S., Ofir, M., & Ginsberg, D.
- Affiliations
- Bar-Ilan University (IL)
- Corresponding author
- Ginsberg, D
- ORCID
- Ginsberg, D
- Venue
- Oncogene
- Published
- 2008-04-14
- Volume
- 27
- Issue
- 35
- Pages
- 4860-4864
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2029327556
- Cited by
- 260
- References
- 23
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 2 · 2023: 12 · 2022: 16 · 2021: 19 · 2020: 16 · 2019: 11 · 2018: 18 · 2017: 15 · 2016: 20 · 2015: 20 · 2014: 12 · 2013: 17 · 2012: 16
- FWCI
- 13.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Israel Cancer Association
- Israel Science Foundation
- Ministry of Health, State of Israel
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- E2F1, autophagy, retinoblastoma pathway, LC3, Atg1, ATG5, DRAM, transcriptional regulation, cell death
- MeSH terms
- Autophagy, Cell Line, Humans, Transcription, Genetic, Oligonucleotide Array Sequence Analysis, E2F1 Transcription Factor
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
