First Author | Strappazzon F | Year | 2010 |
Journal | Biochem Biophys Res Commun | Volume | 397 |
Issue | 1 | Pages | 64-9 |
PubMed ID | 20471954 | Mgi Jnum | J:162431 |
Mgi Id | MGI:4818863 | Doi | 10.1016/j.bbrc.2010.05.062 |
Citation | Strappazzon F, et al. (2010) Alix is involved in caspase 9 activation during calcium-induced apoptosis. Biochem Biophys Res Commun 397(1):64-9 |
abstractText | 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. |