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Alix is involved in caspase 9 activation during calcium-induced apoptosis.

Abstract : 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.
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Submitted on : Thursday, July 8, 2010 - 1:32:52 PM
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Flavie Strappazzon, Sakina Torch, Christine Chatellard-Causse, Anne Petiot, Chantal Thibert, et al.. Alix is involved in caspase 9 activation during calcium-induced apoptosis.. Biochemical and Biophysical Research Communications, Elsevier, 2010, 397 (1), pp.64-9. ⟨10.1016/j.bbrc.2010.05.062⟩. ⟨inserm-00498756⟩



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