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Endoplasmic reticulum stress-induced cell death mediated by the proteasome.

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.

SUBMITTER: Egger L

PROVIDER: S-EPMC2748804 | biostudies-literature | 2007 Jun

REPOSITORIES: biostudies-literature

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Endoplasmic reticulum stress-induced cell death mediated by the proteasome.

Egger L L Madden D T DT Rhême C C Rao R V RV Bredesen D E DE

Cell death and differentiation 20070330 6

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 exposur ...[more]

PMID: 17396132

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