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
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, P.H.S.
MeSH terms
- Amino Acid Sequence
- Animals
- Apoptosis Regulatory Proteins
- Apoptosis* / drug effects
- Apoptosis* / radiation effects
- Bcl-2-Like Protein 11
- Binding Sites
- Carrier Proteins / chemistry
- Carrier Proteins / genetics
- Carrier Proteins / metabolism*
- Caspase Inhibitors
- Caspases / metabolism
- Cell Line
- Dimerization
- Drosophila Proteins*
- Dyneins
- Gene Library
- Humans
- Membrane Proteins*
- Mice
- Microtubules / metabolism
- Molecular Motor Proteins / metabolism*
- Molecular Sequence Data
- Mutation
- Precipitin Tests
- Protein Binding
- Protein Isoforms / genetics
- Protein Isoforms / metabolism
- Proto-Oncogene Proteins c-bcl-2 / metabolism
- Proto-Oncogene Proteins*
- Saccharomyces cerevisiae / genetics
Substances
- Apoptosis Regulatory Proteins
- BCL2L11 protein, human
- Bcl-2-Like Protein 11
- Bcl2l11 protein, mouse
- Carrier Proteins
- Caspase Inhibitors
- Drosophila Proteins
- Membrane Proteins
- Molecular Motor Proteins
- Protein Isoforms
- Proto-Oncogene Proteins
- Proto-Oncogene Proteins c-bcl-2
- Caspases
- Dyneins