The C-terminus of bax is not a membrane addressing/anchoring signal.
It has been suggested that BCL-2 family members associate with certain organelles through their hydrophobic C-terminus which in the case of bcl-2, appears to play a key role in the regulation of apoptosis. We have investigated the association of bax with microsomal, nuclear and mitochondrial membranes using a cell-free system and found, contrary to bcl-2, that bax binds poorly to these organelles. Deletion of the C-terminal of bax (baxDeltaC) or exchanging the C-terminal ends of bax and bcl-XL suggests that the bax C-terminus is not an addressing/anchoring signal. In agreement with this observation, HL-60 cells transfected with either bax or baxDeltaC show no difference in sensitivity to an apoptotic signal. In the cell-free system, at low pH, bax becomes associated with mitochondria after a change of conformation, a result consistant with its structural homology with certain bacterial toxins. In HL-60 cells, as observed in the cell-free system, bax acquired a protease resistant conformation upon its translocation from the cytosol to the mitochondria after the induction of apoptosis.
Tremblais
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Unité INSERM 419, 9 Quai Moncousu, Nantes Cedex 01, 44035, France.
Oliver
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Juin
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Le Cabellec
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Meflah
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Vallette
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D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D004317:Doxorubicin / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000166:cytology; D008861:Microsomes / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D010179:Pancreas / Q000166:cytology; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C494828:Bax protein, rat; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D051028:bcl-2-Associated X Protein; D004317:Doxorubicin