Endoplasmic reticulum stress-induced cell death mediated by the proteasome |
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Authors: | Egger L Madden D T Rhême C Rao R V Bredesen D E |
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Institution: | The Buck Institute for Age Research, Novato, CA 94945, USA. lotti.egger@bluemail.ch |
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Abstract: | Cells exposed to sustained endoplasmic reticulum (ER) stress undergo programmed cell death and display features typical of apoptosis, such as cysteine aspartyl protease (caspase) activation, cytochrome c release, and DNA fragmentation. Here, we show that the execution of cell death induced by ER stress is mediated via the proteasome. Inhibition of the proteasome by lactacystin prevented ER stress-induced degradation of Bcl-2, release of cytochrome c, processing of effector caspase-3, and exposure of phosphatidylserine. Owing to the ability of lactacystin to inhibit cytochrome c release, we propose that the pro-apoptotic activity of the proteasome lies upstream of mitochondrial activation. Thus, the proteasome serves as a principal mediator of ER stress-induced cell death in this system. |
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