Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis.
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.
Puthalakath
H
H
The Walter and Eliza Hall Institute of Medical Research, Melbourne, P.O. Royal Melbourne Hospital, 3050 VIC, Australia.
Villunger
A
A
O'Reilly
L A
LA
Beaumont
J G
JG
Coultas
L
L
Cheney
R E
RE
Huang
D C
DC
Strasser
A
A
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D023102:Anoikis; D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism; D029721:Drosophila Proteins; D004398:Dyneins; D020869:Gene Expression Profiling; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D020409:Molecular Motor Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D024701:Myosin Type V; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D014162:Transfection; D020798:Two-Hybrid System Techniques
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; C486655:BMF protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; C435486:Bmf protein, mouse; D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D029721:Drosophila Proteins; D008565:Membrane Proteins; D020409:Molecular Motor Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C078829:chicken brain myosin-V p190; D024701:Myosin Type V; D004398:Dyneins