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Science 293 (5536): 1829-1832

Copyright © 2001 by the American Association for the Advancement of Science

Bmf: A Proapoptotic BH3-Only Protein Regulated by Interaction with the Myosin V Actin Motor Complex, Activated by Anoikis

Hamsa Puthalakath,1 Andreas Villunger,1 Lorraine A. O'Reilly,1 Jennifer G. Beaumont,1 Leigh Coultas,1 Richard E. Cheney,2 David C. S. Huang,1 Andreas Strasser1*

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.

1 The Walter and Eliza Hall Institute of Medical Research, Melbourne, P.O. Royal Melbourne Hospital, 3050 VIC, Australia.
2 University of North Carolina, Chapel Hill, NC 27599-7545, USA
*   To whom correspondence should be addressed. E-mail: strasser{at}

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K. Lei and R. J. Davis (2003)
PNAS 100, 2432-2437
   Abstract »    Full Text »    PDF »
Tankyrase 1 Interacts with Mcl-1 Proteins and Inhibits Their Regulation of Apoptosis.
J. Bae, J. R. Donigian, and A. J. W. Hsueh (2003)
J. Biol. Chem. 278, 5195-5204
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14-3-3 Interacts Directly with and Negatively Regulates Pro-apoptotic Bax.
M. Nomura, S. Shimizu, T. Sugiyama, M. Narita, T. Ito, H. Matsuda, and Y. Tsujimoto (2003)
J. Biol. Chem. 278, 2058-2065
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Advances in Biology and Therapy of Multiple Myeloma.
S. Barille-Nion, B. Barlogie, R. Bataille, P. L. Bergsagel, J. Epstein, R. G. Fenton, J. Jacobson, W. M. Kuehl, J. Shaughnessy, and G. Tricot (2003)
Hematology 2003, 248-278
   Abstract »    Full Text »    PDF »
Cell Detachment Triggers p38 Mitogen-activated Protein Kinase-dependent Overexpression of Fas Ligand. A NOVEL MECHANISM OF ANOIKIS OF INTESTINAL EPITHELIAL CELLS.
K. Rosen, W. Shi, B. Calabretta, and J. Filmus (2002)
J. Biol. Chem. 277, 46123-46130
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DAP-kinase induces apoptosis by suppressing integrin activity and disrupting matrix survival signals.
W.-J. Wang, J.-C. Kuo, C.-C. Yao, and R.-H. Chen (2002)
J. Cell Biol. 159, 169-179
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Induction of Apoptosis by Stomach Cancer-associated Protein-tyrosine Phosphatase-1.
T. Takada, T. Noguchi, K. Inagaki, T. Hosooka, K. Fukunaga, T. Yamao, W. Ogawa, T. Matozaki, and M. Kasuga (2002)
J. Biol. Chem. 277, 34359-34366
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Gephyrin Interacts with Dynein Light Chains 1 and 2, Components of Motor Protein Complexes.
J. C. Fuhrmann, S. Kins, P. Rostaing, O. El Far, J. Kirsch, M. Sheng, A. Triller, H. Betz, and M. Kneussel (2002)
J. Neurosci. 22, 5393-5402
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Bcl-2 Family Member Bfl-1/A1 Sequesters Truncated Bid to Inhibit Its Collaboration with Pro-apoptotic Bak or Bax.
A. B. Werner, E. de Vries, S. W. G. Tait, I. Bontjer, and J. Borst (2002)
J. Biol. Chem. 277, 22781-22788
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BH-3-only BIK Functions at the Endoplasmic Reticulum to Stimulate Cytochrome c Release from Mitochondria.
M. Germain, J. P. Mathai, and G. C. Shore (2002)
J. Biol. Chem. 277, 18053-18060
   Abstract »    Full Text »    PDF »

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