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

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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  • Becn1 haploinsufficient mice develop tumours, indicating autophagy might act as an important in vivo tumour suppressor.

    “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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Authors
Yue, Z., Jin, S., Yang, C., Levine, A. J., & Heintz, N.
Affiliations
Howard Hughes Medical Institute (US)
ORCID
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
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
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 › 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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