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PMID:14657337

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Citation

Yue, Z, Jin, S, Yang, C, Levine, AJ and Heintz, N (2003) Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc. Natl. Acad. Sci. U.S.A. 100:15077-82

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.

Links

PubMed PMC299911 Online version:10.1073/pnas.2436255100

Keywords

Animals; Apoptosis; Apoptosis Regulatory Proteins; Autophagy; Embryo, Mammalian/cytology; Gene Deletion; Genes, Tumor Suppressor; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mice, Transgenic; Microscopy, Electron; Models, Genetic; Mutation; Neoplasms/metabolism; Proteins/genetics; Proteins/physiology; RNA, Messenger/metabolism; Time Factors; Ultraviolet Rays

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


See also

References

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