Proteolytic control of regulated necrosis

Proteases control most of the physiological processes that occur in a cell. This particularly applies to apoptosis, the most well-studied form of cell death, where proteolysis by cysteine-aspartic proteases (caspases) is the primary mechanism for both initiation and execution of cell suicide. In contrast, the impact of proteolysis on other, non-apoptotic cell death pathways (summarized under the term “regulated necrosis”, RN) has long been enigmatic, but has clearly been confirmed by a number of recent groundbreaking discoveries. Here, we review these discoveries and provide an overview on the role of proteolysis in known forms of RN, with a particular focus on necroptosis and pyroptosis, and their regulation by deubiquitinases, apoptotic and inflammatory caspases. This article is part of a Special Issue entitled: Proteolysis as a Regulatory Event in Pathophysiology edited by Stefan Rose-John.