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

Z Yue, S Jin, C Yang, AJ Levine… - Proceedings of the …, 2003 - National Acad Sciences
Z Yue, S Jin, C Yang, AJ Levine, N Heintz
Proceedings of the National Academy of Sciences, 2003National Acad Sciences
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 …
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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