Redistribution of Bax from cytosol to membranes is induced by apoptotic stimuli and is an early step in the apoptotic pathway.
It is known that overexpression of Bax accelerates apoptosis, but the biochemical mechanism of the signal transduction from Bax to downstream targets has still not been fully determined. In the present study, we demonstrate that upon apoptotic stimuli, Bax moves from the cytosolic to the membrane fraction. The redistribution of Bax is not inhibited by a caspase inhibitor, zVAD-fmk, which blocks caspase-3 activity and prevents apoptosis in vivo. A FL5.12 Bax CL16 mutant cell, ms3, which is resistant to apoptosis induced by staurosporine, retains the activity of Bax redistribution but shows no caspase-3 activity. Our results revealed that Bax accumulation on membranes precedes caspase-3 activation, indicating that redistribution of Bax is an early event in apoptosis. These results suggest that Bax may be functionally significant in the regulation of caspase-3 activation.
Zhang
H
H
Oncology, Molecular Genetics, Novartis Pharma AG, Basel, CH- 4002, Switzerland.
Heim
J
J
Meyhack
B
B
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001402:B-Lymphocytes; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival; D002999:Clone Cells; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation; D019254:Genes, bcl-2; D007377:Interleukin-3 / Q000494:pharmacology / Q000502:physiology; D007700:Kinetics; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D019311:Staurosporine / Q000494:pharmacology; D051028:bcl-2-Associated X Protein
D000590:Amino Acid Chloromethyl Ketones; C494827:Bax protein, mouse; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D019311:Staurosporine