Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor.
Journal:
Proc. Natl. Acad. Sci. U.S.A. 2003 DecAuthors:
Yue Z, Jin S, Yang C, Levine AJ, Heintz N
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 resp
...[more]onse, 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.[less]
Mesh Headings:
Animals, Apoptosis, Apoptosis Regulatory Proteins, Autophagy, Embryo, Mammalian, Gene Deletion, Genes, Tumor Suppressor, Membrane Proteins, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Mice, Transgenic, Microscopy, Electron, Models, Genetic, Mutation, Neoplasms, Proteins, RNA, Messenger, Time Factors, Ultraviolet Rays