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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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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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