Induction of BIM, a proapoptotic BH3-only BCL-2 family member, is critical for neuronal apoptosis
Details
Publication Year 2001-03,Volume 29,Issue #3,Page 615-628
Journal Title
NEURON
Publication Type
Journal Article
Abstract
Sympathetic neuronal death induced by nerve growth factor (NGF) deprivation requires the macromolecular synthesis-dependent translocation of BAX from the cytosol to mitochondria and its subsequent integration into the mitochondrial outer membrane, followed by BAX-mediated cytochrome c (cyt c) release. The gene products triggering this process remain unknown. Here, we report that BIM, a member of the BH3-only proapoptotic subfamily of the BCL-2 protein family, is one such molecule. NGF withdrawal induced expression of BIMEL, an integral mitochondrial membrane protein that functions upstream of (or in parallel with) the BAX/BCL-2 and caspase checkpoints. aim deletion conferred protection against developmental and induced neuronal apoptosis in both central and peripheral populations, but only transiently, suggesting that BIM-and perhaps other BH3-only proteins-serve partially redundant functions upstream of BAX-mediated cyt c release.
Publisher
CELL PRESS
Keywords
NERVE GROWTH-FACTOR; PROGRAMMED CELL-DEATH; TROPHIC-FACTOR DEPRIVATION; CEREBELLAR GRANULE CELLS; DEPENDENT SYMPATHETIC NEURONS; BAX-DEFICIENT MICE; CYTOCHROME-C; PHOSPHATIDYLINOSITOL 3-KINASE; PROTEIN-KINASE; TRANSCRIPTION FACTOR
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Creation Date: 2001-03-01 12:00:00
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