Inhibitors of the ubiquitin-proteasome system are not all alike: identification of a new necrotic pathway

Abstract

In response to stress, cells can not only activate survival pathways, but also death pathways, when the stresses are ungovernable. The case of proteasome impairment is emblematic in this respect. Autophagy is induced, as a prosurvival response, which antagonizes apoptosis. As an additional option, cells can activate necrosis. We have found that certain inhibitors of the ubiquitin-proteasome system can activate a rather peculiar type of necrotic death.