Abstract
Bcl-2 family members that have only a single Bcl-2 homology domain, BH3, are potent inducers of apoptosis, and some appear to play a critical role in developmentally programmed cell death. We examined the regulation of the proapoptotic activity of the BH3-only protein Bim. In healthy cells, most Bim molecules were bound to LC8 cytoplasmic dynein light chain and thereby sequestered to the microtubule-associated dynein motor complex. Certain apoptotic stimuli disrupted the interaction between LC8 and the dynein motor complex. This freed Bim to translocate together with LC8 to Bcl-2 and to neutralize its antiapoptotic activity. This process did not require caspase activity and therefore constitutes an initiating event in apoptosis signaling.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Apoptosis Regulatory Proteins
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Apoptosis* / drug effects
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Apoptosis* / radiation effects
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Bcl-2-Like Protein 11
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Binding Sites
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Caspase Inhibitors
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Caspases / metabolism
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Cell Line
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Dimerization
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Drosophila Proteins*
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Dyneins
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Gene Library
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Humans
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Membrane Proteins*
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Mice
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Microtubules / metabolism
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Molecular Motor Proteins / metabolism*
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Molecular Sequence Data
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Mutation
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Precipitin Tests
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Protein Binding
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Proto-Oncogene Proteins*
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Saccharomyces cerevisiae / genetics
Substances
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Apoptosis Regulatory Proteins
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BCL2L11 protein, human
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Bcl-2-Like Protein 11
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Bcl2l11 protein, mouse
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Carrier Proteins
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Caspase Inhibitors
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Drosophila Proteins
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Membrane Proteins
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Molecular Motor Proteins
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Protein Isoforms
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Caspases
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Dyneins