Inhibitors of the ubiquitin-proteasome system are not all alike: identification of a new necrotic pathway.
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.
Foti
Carmela
C
Dipartimento di Scienze e Tecnologie Biomediche, Universita' Degli Studi di Udine, Piazzale Kolbe 4, Udine, Italy.
Demarchi
Francesca
F
Brancolini
Claudio
C
D000818:Animals; D001343:Autophagy / Q000187:drug effects; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D051379:Mice; D009336:Necrosis / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000032:analysis*; D011719:Pyrazines / Q000494:pharmacology; D025801:Ubiquitin / Q000037:antagonists & inhibitors*
D001897:Boronic Acids; D004791:Enzyme Inhibitors; D011719:Pyrazines; D025801:Ubiquitin; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex