@article{e86e6e87ea1743e7ae1119d0d6bb4498,
title = "Induction of BIM, a proapoptotic BH3-only BCL-2 family member, is critical for neuronal apoptosis",
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. Bim 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.",
author = "Putcha, {Girish V.} and Moulder, {Krista L.} and Golden, {Judith P.} and Philippe Bouillet and Adams, {Jerry A.} and Andreas Strasser and Johnson, {Eugene M.}",
note = "Funding Information: This work was supported by National Institutes of Health grants R37AG-12947 and RO1NS38651 (E. M. J.). We thank S. J. Korsmeyer (Dana Farber Cancer Institute) for Bax - and Bad -deficient mice; J.-C. Martinou (Serono Pharmaceutical Research Institute, Geneva, Switzerland) and S. Tonegawa (Massachusetts Institute of Technology) for the Bcl-2 transgenic mice; A. Maroney (Cephalon, West Chester, PA) for CEP-1347; A. Milligan, J. Merryfull, and S. Kyvetos for animal care; M. C. Wallace, H. L. Fraser, J. T. Gross, M. C. Funk, and P. A. Kraus of the Washington University Neuroscience Transgenic Core Facility for excellent mouse husbandry; P. A. Osborne for assistance with neuronal dissections; C. A. Harris for assistance with CEP-1347 experiments; P. M. Rich for help with cell counts; M. Bloomgren for secretarial assistance; and members of the Johnson lab for their critical review of this manuscript. ",
year = "2001",
doi = "10.1016/S0896-6273(01)00238-0",
language = "English",
volume = "29",
pages = "615--628",
journal = "Neuron",
issn = "0896-6273",
number = "3",
}