One explanation for why the development of cancer cells is a relatively rare event is that cells that lose their attachment to a substratum and associated integrin signaling often undergo cell death or apoptosis. Puthalakath et al. now describe a mechanism by which unattached cells may sense changes in the cytoskeleton and may initiate the process of apoptosis. A new mammalian Bcl-2 family member called Bmf can promote apoptosis by binding to and inhibiting the prosurvival Bcl-2 proteins. Bmf interacts with dynein light chain 2 and becomes localized to the myosin V motor complex on filamentous actin. In cells in which the actin cytoskeleton was disrupted by treatment with actin-depolymerizing agents or by culture of the cells in suspension (without attachment to a substratum), Bmf was released from its association with the cytoskelton and freed to interact with Bcl-2. Thus, Bmf appears to function as a sensor that couples alterations in the cytoskeleton to activation of the cell death machinery. See the Perspective by Hunt and Evan for more details.
H. Puthalakath, A. Villunger, L. A. O'Reilly, J. G. Beaumont, L. Coultas, R. E. Cheney, D. C. S. Huang, A Strasser, Bmf: A proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis. Science 293, 1829-1832 (2001). [Abstract] [Full Text]
A. Hunt, G. Evan, Till death us do part. Science 293, 1784-1785 (2001). [Full Text]