Alix is involved in caspase 9 activation during calcium-induced apoptosis.
The cytoplasmic protein Alix/AIP1 (ALG-2 interacting protein X) is involved in cell death through mechanisms which remain unclear but require its binding partner ALG-2 (apoptosis-linked gene-2). The latter was defined as a regulator of calcium-induced apoptosis following endoplasmic reticulum (ER) stress. We show here that Alix is also a critical component of caspase 9 activation and apoptosis triggered by calcium. Indeed, expression of Alix dominant-negative mutants or downregulation of Alix afford significant protection against cytosolic calcium elevation following thapsigargin (Tg) treatment. The function of Alix in this paradigm requires its interaction with ALG-2. In addition, we demonstrate that caspase 9 activation is necessary for apoptosis induced by Tg and that this activation is impaired by knocking down Alix. Altogether, our findings identify, for the first time, Alix as a crucial mediator of Ca(2+) induced caspase 9 activation.
Strappazzon
Flavie
F
INSERM U836, Grenoble, France.
Torch
Sakina
S
Chatellard-Causse
Christine
C
Petiot
Anne
A
Thibert
Chantal
C
Blot
Béatrice
B
Verna
Jean-Marc
JM
Sadoul
Rémy
R
D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D019284:Thapsigargin / Q000494:pharmacology
D002135:Calcium-Binding Proteins; D004791:Enzyme Inhibitors; C492144:Pdcd6ip protein, mouse; D019284:Thapsigargin; D053453:Caspase 9; D002118:Calcium