Abstract
Bcl-2 family members bearing only the BH3 domain are essential inducers of apoptosis. We identified a BH3-only protein, Bmf, and show that its BH3 domain is required both for binding to prosurvival Bcl-2 proteins and for triggering apoptosis. In healthy cells, Bmf is sequestered to myosin V motors by association with dynein light chain 2. Certain damage signals, such as loss of cell attachment (anoikis), unleash Bmf, allowing it to translocate and bind prosurvival Bcl-2 proteins. Thus, at least two mammalian BH3-only proteins, Bmf and Bim, function to sense intracellular damage by their localization to distinct cytoskeletal structures.
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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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Animals
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Anoikis*
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Apoptosis Regulatory Proteins
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Bcl-2-Like Protein 11
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Calmodulin-Binding Proteins / metabolism*
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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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Cell Line
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Cytoskeleton / metabolism
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Drosophila Proteins*
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Dyneins
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Gene Expression Profiling
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Humans
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Membrane Proteins*
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Mice
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Molecular Motor Proteins / metabolism*
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Molecular Sequence Data
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Mutation
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Myeloid Cell Leukemia Sequence 1 Protein
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Myosin Type V*
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism
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Nerve Tissue Proteins / metabolism*
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Protein Binding
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Protein Structure, Tertiary
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Protein Transport
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Proto-Oncogene Proteins c-bcl-2 / chemistry
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Proto-Oncogene Proteins*
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RNA, Messenger / analysis
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RNA, Messenger / genetics
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Transfection
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Two-Hybrid System Techniques
Substances
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Adaptor Proteins, Signal Transducing
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Apoptosis Regulatory Proteins
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BCL2L11 protein, human
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BMF protein, human
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Bcl-2-Like Protein 11
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Bcl2l11 protein, mouse
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Bmf protein, mouse
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Calmodulin-Binding Proteins
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Carrier Proteins
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Drosophila Proteins
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Membrane Proteins
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Molecular Motor Proteins
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Myeloid Cell Leukemia Sequence 1 Protein
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Neoplasm Proteins
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Nerve Tissue Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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RNA, Messenger
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chicken brain myosin-V p190
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Myosin Type V
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Dyneins
Associated data
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GENBANK/AY029253
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GENBANK/AY029254
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GENBANK/AY029255