Cited by 2,116Autophagy in Disease and TherapyCancer-related Molecular PathwaysCell death mechanisms and regulation

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Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor

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Yue, Zhenyu, Jin, Shengkan, Yang, Chingwen, Levine, Arnold J., Heintz, Nathaniel·2003·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.2436255100PMC PMC299911

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Abstract

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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Authors: Yue, Z., Jin, S., Yang, C., Levine, A. J., & Heintz, N.
Affiliations: Howard Hughes Medical Institute (US)
ORCID: Yue, Zhenyu
Levine, Arnold J.
Heintz, Nathaniel
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
DOI: 10.1073/pnas.2436255100
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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Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor

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