The substitution of the C-terminus of bax by that of bcl-xL does not affect its subcellular localization but abrogates its pro-apoptotic properties.
The interaction of the anti-apoptotic members of the Bcl-2 family with mitochondria, through their hydrophobic C-terminus, has been proposed to play a crucial role in the execution phase of apoptosis. We report here that a substitution of the C-terminal end of pro-apoptotic bax by that of anti-apoptotic bcl-xL (baxCxL) does not modify its association with mitochondria in human and rat cells or in Saccharomyces cerevisiae. In addition, while bax sensitizes these cells to apoptotic stimuli, the construct baxCxL does not affect the apoptotic response in transfected cells. These results suggest that the C-terminus of bax plays an important role in apoptosis independently of its membrane addressing/targeting mechanism.
Oliver
L
L
Unité INSERM 419, Nantes Cedex 1, France.
Priault
M
M
Tremblais
K
K
LeCabellec
M
M
Meflah
K
K
Manon
S
S
Vallette
F M
FM
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D002462:Cell Membrane / Q000502:physiology; D003600:Cytosol / Q000502:physiology; D005910:Glioma; D006801:Humans; D020014:K562 Cells; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008928:Mitochondria / Q000502:physiology; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000502:physiology; D017384:Sequence Deletion; D014162:Transfection; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494826:BAX protein, human; C494811:BCL2L1 protein, human; C494828:Bax protein, rat; C494813:Bcl2l1 protein, rat; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D007770:L-Lactate Dehydrogenase; D010447:Peptide Hydrolases; C108711:DEVDase