Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor.
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.
Pubmed ID: 14657337 RIS Download
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