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Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor
Open accessAbstract
The biochemical properties of beclin 1 suggest a role in two fundamentally important cell biological pathways: autophagy and apoptosis. We show here that beclin 1 -/- mutant mice die early in embryogenesis and beclin 1 +/- mutant mice suffer from a high incidence of spontaneous tumors. These tumors continue to express wild-type beclin 1 mRNA and protein, establishing that beclin 1 is a haploinsufficient tumor suppressor gene. Beclin 1 -/- embryonic stem cells have a severely altered autophagic response, whereas their apoptotic response to serum withdrawal or UV light is normal. These results demonstrate that beclin 1 is a critical component of mammalian autophagy and establish a role for autophagy in tumor suppression. They both provide a biological explanation for recent evidence implicating beclin 1 in human cancer and suggest that mutations in other genes operating in this pathway may contribute to tumor formation through deregulation of autophagy.
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“In this case, the haploinsufficient mice developed tumours, indicating that autophagy might act as an important in vivo tumour suppressor 76, 77 .”
From The common biology of cancer and ageing (2007) · cites this paper as [76]
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Cites
Autophagy as a Regulated Pathway of Cellular Degradation
Klionsky, D. J., & Emr, S. D. (2000) · Science · doi:10.1126/science.290.5497.1717 · Cited by 3,630
Induction of autophagy and inhibition of tumorigenesis by beclin 1
Liang, X. H., Jackson, S., Seaman, M., Brown, K., Kempkes, B., Hibshoosh, H., & Levine, B. (1999) · Nature · doi:10.1038/45257 · Cited by 3,347
TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
Inoki, K., Li, Y., Zhu, T., Wu, J., & Guan, K.-L. (2002) · Nature Cell Biology · doi:10.1038/ncb839 · Cited by 3,083
Cantley, L. C., & Neel, B. G. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.8.4240 · Cited by 2,018
The Atlas of Mouse Development
Kaufman, M. H. (1992) · Medical Entomology and Zoology · Cited by 1,750
Pten is essential for embryonic development and tumour suppression
Cristofano, A. D., Pesce, B., Cordon‐Cardo, C., & Pandolfi, P. P. (1998) · Nature Genetics · doi:10.1038/1235 · Cited by 1,518
Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death
Joza, N. A., Susín, S. A., Daugas, É., Stanford, W. L., Cho, S. K., Li, C. Y. J., Sasaki, T., Elia, A., Cheng, H.-Y. M., Ravagnan, L., et al. (2001) · Nature · doi:10.1038/35069004 · Cited by 1,393
Dissection of Autophagosome Formation Using Apg5-Deficient Mouse Embryonic Stem Cells
Mizushima, N., Yamamoto, A., Hatano, M., Kobayashi, Y., Kabeya, Y., Suzuki, K., Tokuhisa, T., Ohsumi, Y., & Yoshimori, T. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.152.4.657 · Cited by 1,361
Molecular dissection of autophagy: two ubiquitin-like systems
Ohsumi, Y. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35056522 · Cited by 1,240
Protection against Fatal Sindbis Virus Encephalitis by Beclin, a Novel Bcl-2-Interacting Protein
Liang, X. H., Kleeman, L. K., Jiang, H., Gordon, G. W., Goldman, J. E., Berry, G., Herman, B. A., & Levine, B. (1998) · Journal of Virology · doi:10.1128/jvi.72.11.8586-8596.1998 · Cited by 1,128
Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E
Fingar, D. C., Salama, S., Tsou, C., Harlow, E., & Blenis, J. (2002) · Genes & Development · doi:10.1101/gad.995802 · Cited by 1,093
Lawlor, M. A., & Alessi, D. R. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.16.2903 · Cited by 1,068
AKT plays a central role in tumorigenesis
Testa, J. R., & Bellacosa, A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.211430998 · Cited by 944
Nevins, J. R. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.7.699 · Cited by 939
Cloning and Genomic Organization of Beclin 1, a Candidate Tumor Suppressor Gene on Chromosome 17q21
Aita, V. M., Liang, X. H., Murty, V. V. V. S., Pincus, D. L., Yu, W., Cayanis, E., Kalachikov, S. M., Gilliam, T. C., & Levine, B. (1999) · Genomics · doi:10.1006/geno.1999.5851 · Cited by 800
Mechanisms of p53-dependent apoptosis
Schuler, M., & Green, D. R. (2001) · Biochemical Society Transactions · doi:10.1042/bst0290684 · Cited by 641
The autophagosomal–lysosomal compartment in programmed cell death
Bursch, W. (2001) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400852 · Cited by 620
Arico, S., Petiot, A., Bauvy, C., Dubbelhuis, P. F., Meijer, A. J., Codogno, P., & Ogier‐Denis, É. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c100319200 · Cited by 591
Ilić, D., Almeida, E. A. C., Schlaepfer, D. D., Dazin, P., Aizawa, S., & Damsky, C. H. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.143.2.547 · Cited by 495
Xue, L., Fletcher, G. C., & Tolkovsky, A. M. (1999) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.1999.0780 · Cited by 429
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 383
Autophagy: a barrier or an adaptive response to cancer
Ogier‐Denis, É., & Codogno, P. (2003) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/s0304-419x(03)00004-0 · Cited by 370
A Novel Protein Complex Linking the δ2 Glutamate Receptor and Autophagy
Yue, Z., Horton, A., Bravin, M., DeJager, P. L., Selimi, F., & Heintz, N. (2002) · Neuron · doi:10.1016/s0896-6273(02)00861-9 · Cited by 306
Self-citationp53 transcriptional activity is essential for p53‐dependent apoptosis following DNA damage
Chao, C., Saito, S., Kang, J., Anderson, C. W., Appella, E., & Xu, Y. (2000) · The EMBO Journal · doi:10.1093/emboj/19.18.4967 · Cited by 260
Kalantry, S., Manning, S., Haub, O., Tomihara-Newberger, C., Lee, H.-G., Fangman, J., Distèche, C. M., Manova, K., & Lacy, E. (2001) · Nature Genetics · doi:10.1038/86912 · Cited by 138
Reduced autophagic activity in primary rat hepatocellular carcinoma and ascites hepatoma cells
Kisen, G. O., Tessitore, L., Costelli, P., Gordon, P. B., Schwarze, P. E., Baccino, F. M., & Seglen, P. O. (1993) · Carcinogenesis · doi:10.1093/carcin/14.12.2501 · Cited by 132
Ets1 is required for p53 transcriptional activity in UV‐induced apoptosis in embryonic stem cells
Xu, D., Wilson, T. J., Chan, D., Luca, E. D., Zhou, J., Hertzog, P. J., & Kola, I. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf413 · Cited by 82
Khalfan, W., & Klionsky, D. J. (2002) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(02)00343-5 · Cited by 69
Manova, K., Tomihara-Newberger, C., Wang, S., Godelman, A., Kalantry, S., Whitty, K. B., Leon, V. D., Chen, W. S., Lacy, E., & Bachvarova, R. F. (1998) · Developmental Dynamics · doi:10.1002/(sici)1097-0177(199811)213:3 · Cited by 56
Rossant, J., & Cross, J. C. (2002) · Elsevier eBooks · doi:10.1016/b978-012597951-1/50011-1 · Cited by 18
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- Ogier-Denis, E. & Codogno, P. (2003) Biochim. Biophys. Acta 1603, 113-128.12618311
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Li, Y., Jiang, Q. L., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,351
Autophagy in the Pathogenesis of Disease
Levine, B., & Kroemer, G. (2008) · Cell · doi:10.1016/j.cell.2007.12.018 · Cited by 7,069
Autophagy fights disease through cellular self-digestion
Mizushima, N., Levine, B., Cuervo, A. M., & Klionsky, D. J. (2008) · Nature · doi:10.1038/nature06639 · Cited by 6,452
Autophagy: Renovation of Cells and Tissues
Mizushima, N., & Komatsu, M. (2011) · Cell · doi:10.1016/j.cell.2011.10.026 · Cited by 6,615
Methods in Mammalian Autophagy Research
Mizushima, N., Yoshimori, T., & Levine, B. (2010) · Cell · doi:10.1016/j.cell.2010.01.028 · Cited by 4,497
Metadata
- Authors
- Yue, Z., Jin, S., Yang, C., Levine, A. J., & Heintz, N.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2003-12
- Volume
- 100
- Issue
- 25
- Pages
- 15077-15082
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC299911
- OpenAlex
- W2066800765
- Cited by
- 2,116
- References
- 30
- Citations by year
- 2026: 28 · 2025: 51 · 2024: 74 · 2023: 70 · 2022: 89 · 2021: 105 · 2020: 113 · 2019: 106 · 2018: 103 · 2017: 107 · 2016: 115 · 2015: 133 · 2014: 120 · 2013: 168 · 2012: 132
- FWCI
- 25.54
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- Beclin-1, autophagy, haploinsufficiency, tumor suppressor, early embryonic development, embryonic lethality, spontaneous tumors, apoptosis, embryonic stem cells, UV-induced apoptosis, serum deprivation, cancer
- MeSH terms
- Beclin-1, Animals, Autophagy, Embryo, Mammalian, Membrane Proteins, Mice, Inbred C57BL, Mice, Mutant Strains, Mice, Transgenic, Microscopy, Electron, Models, Genetic, Mutation, Neoplasms, Proteins, RNA, Messenger, Time Factors, Ultraviolet Rays, Genes, Tumor Suppressor, Apoptosis, Gene Deletion, Apoptosis Regulatory Proteins, Mice
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