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Bmf: A Proapoptotic BH3-Only Protein Regulated by Interaction with the Myosin V Actin Motor Complex, Activated by Anoikis
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.
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“At least in some settings, detachment from the extracellular matrix triggers MOMP upon activation of the BH3-only proteins BIM and BMF [137, 235].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [137]
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Research works printed but not linked: 4
- H. Puthalakath D. C. S. Huang L. A. O'Reilly
- Supplementary material is available on Science Online at www.sciencemag.org/cgi/content/full/293/5536/1829/DC1
- Wick W., et al., Oncogene 12, 973 (1996).
- We thank L. O'Connor and K. Newton for help with experiments and sequence analysis L. Cullen and S. Novakovic for expert technical assistance J. Visvader and W. Alexander for reagents and G. Filby for editorial assistance. We are grateful to J. Adams P. Bouillet A. Harris and S. Cory for critical review of the manuscript. This work was supported by fellowships and grants from the National Health and Medical Research Council (Canberra; Reg. Key 973002) the U.S. National Cancer Institute (CA 80188) the Dr Josef Steiner Cancer Research Foundation the Leukemia and Lymphoma Society of America the Human Frontiers Science Program and the Sylvia and Charles Viertel Charitable Foundation. The sequences for mouse bmf human bmf and mouse dlc 2 have been deposited with GenBank (accession numbers: and respectively).
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Metadata
- Authors
- Puthalakath, H., Villunger, A., O'Reilly, L. A., Beaumont, J. G., Coultas, L., Cheney, R. E., Huang, D. C. S., & Strasser, A.
- Affiliations
- The Royal Melbourne Hospital (AU)
- The Walter and Eliza Hall Institute of Medical Research, Melbourne, P.O. Royal Melbourne Hospital, 3050 VIC, Australia.
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Strasser, Andreas
- ORCID
- Venue
- Science
- Published
- 2001-09-07
- Volume
- 293
- Issue
- 5536
- Pages
- 1829-1832
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1993059855
- Cited by
- 656
- References
- 24
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 13 · 2023: 16 · 2022: 12 · 2021: 41 · 2020: 10 · 2019: 15 · 2018: 15 · 2017: 13 · 2016: 18 · 2015: 23 · 2014: 14 · 2013: 25 · 2012: 27
- FWCI
- 15.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (#CA 80188, R01CA080188)
- National Institute on Deafness and Other Communication Disorders (R29DC003299)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- BMF, BH3-only proteins, apoptosis, myosin V, anoikis, Bcl-2 family proteins, cytoskeleton, building information modeling, protein translocation
- MeSH terms
- Bcl-2-Like Protein 11, Amino Acid Sequence, Animals, Calmodulin-Binding Proteins, Carrier Proteins, Cell Line, Cytoskeleton, Dyneins, Humans, Membrane Proteins, Molecular Sequence Data, Mutation, Neoplasm Proteins, Nerve Tissue Proteins, Protein Binding, Proto-Oncogene Proteins, RNA, Messenger, Transfection, Protein Structure, Tertiary, Proto-Oncogene Proteins c-bcl-2, Molecular Motor Proteins, Two-Hybrid System Techniques, Gene Expression Profiling, Protein Transport, Anoikis, Myosin Type V, Drosophila Proteins, Adaptor Proteins, Signal Transducing, Apoptosis Regulatory Proteins, Mice, Myeloid Cell Leukemia Sequence 1 Protein
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