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

Zhenyu Yue; Xin Jin; Chingwen Yang; Arnold J. Levine; Nathaniel Heintz

doi:10.1073/pnas.2436255100

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.

Keywords

AutophagyHaploinsufficiencyBiologyCell biologyEmbryonic stem cellSuppressorCarcinogenesisTumor suppressor geneMutantCancer researchApoptosisGeneGeneticsPhenotype

MeSH Terms

AnimalsApoptosisApoptosis Regulatory ProteinsAutophagyBeclin-1EmbryoMammalianGene DeletionGenesTumor SuppressorMembrane ProteinsMiceMiceInbred C57BLMiceMutant StrainsMiceTransgenicMicroscopyElectronModelsGeneticMutationNeoplasmsProteinsRNAMessengerTime FactorsUltraviolet Rays

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Publication Info

Year: 2003
Type: article
Volume: 100
Issue: 25
Pages: 15077-15082
Citations: 2067
Access: Closed

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APA Style

                            
                                
                                    Zhenyu Yue, 
                                
                                    Xin Jin, 
                                
                                    Chingwen Yang
                                
                                et al.
                            
                            (2003). 
                            Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. 
                            Proceedings of the National Academy of Sciences
                            , 100
                            (25)
                            , 15077-15082.
                            https://doi.org/10.1073/pnas.2436255100
                        

Identifiers

DOI: 10.1073/pnas.2436255100
PMID: 14657337
PMCID: PMC299911

Data Quality

Data completeness: 86%