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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}wehi.edu.au



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   Abstract »    Full Text »    PDF »
Cell Stress-Associated Caspase Activation: Intrinsically Complex?.
E. M. Creagh and S. J. Martin (2003)
Sci. STKE 2003, pe11
   Abstract »    Full Text »    PDF »
Essential role for the BH3-only protein Bim but redundant roles for Bax, Bcl-2, and Bcl-w in the control of granulocyte survival.
A. Villunger, C. Scott, P. Bouillet, and A. Strasser (2003)
Blood 101, 2393-2400
   Abstract »    Full Text »    PDF »
JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis.
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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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