Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis

Science. 2001 Sep 7;293(5536):1829-32. doi: 10.1126/science.1062257.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Animals
  • Anoikis*
  • Apoptosis Regulatory Proteins
  • Bcl-2-Like Protein 11
  • Calmodulin-Binding Proteins / metabolism*
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line
  • Cytoskeleton / metabolism
  • Drosophila Proteins*
  • Dyneins
  • Gene Expression Profiling
  • Humans
  • Membrane Proteins*
  • Mice
  • Molecular Motor Proteins / metabolism*
  • Molecular Sequence Data
  • Mutation
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Myosin Type V*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Nerve Tissue Proteins / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Transport
  • Proto-Oncogene Proteins c-bcl-2 / chemistry
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins*
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Transfection
  • Two-Hybrid System Techniques

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • BCL2L11 protein, human
  • BMF protein, human
  • Bcl-2-Like Protein 11
  • Bcl2l11 protein, mouse
  • Bmf protein, mouse
  • Calmodulin-Binding Proteins
  • Carrier Proteins
  • Drosophila Proteins
  • Membrane Proteins
  • Molecular Motor Proteins
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • chicken brain myosin-V p190
  • Myosin Type V
  • Dyneins

Associated data

  • GENBANK/AY029253
  • GENBANK/AY029254
  • GENBANK/AY029255