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Bmf: A Proapoptotic BH3-Only Protein Regulated by Interaction with the Myosin V Actin Motor Complex, Activated by Anoikis
Hamsa Puthalakath,1Andreas Villunger,1Lorraine A. O'Reilly,1Jennifer G. Beaumont,1Leigh Coultas,1Richard E. Cheney,2David C. S. Huang,1Andreas 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 prosurvivalBcl-2
proteins and for triggering apoptosis. In healthy cells,Bmf is
sequestered to myosin V motors by association with dyneinlight chain
2. Certain damage signals, such as loss of cell attachment(anoikis),
unleash Bmf, allowing it to translocate and bind prosurvivalBcl-2
proteins. Thus, at least two mammalian BH3-only proteins,Bmf and Bim,
function to sense intracellular damage by their localizationto
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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Abigail Hunt and Gerard Evan (7 September 2001) Science293 (5536), 1784.
[DOI: 10.1126/science.1065206] |Summary »|Full Text »|PDF »
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|Abstract »|Full Text »|PDF »
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J. Biol. Chem.
278, 2058-2065
|Abstract »|Full Text »|PDF »
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|Abstract »|Full Text »|PDF »
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