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

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

¹The Walter and Eliza Hall Institute of Medical Research, Melbourne, P.O. Royal Melbourne Hospital, 3050 VIC, Australia. ²University of North Carolina, Chapel Hill, NC 27599-7545, USA

*To whom correspondence should be addressed. E-mail: [email protected]

4 May 2001; accepted 11 July 2001

Science 293(5536):p 1829-1832, September 7, 2001.

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.