Protease signalling in cell death: caspases versus cysteine cathepsins☆

Abstract 

Proteases were, for a long time, mainly considered as protein degrading enzymes. However, in the last decade this view has changed dramatically, and the focus is now on proteases as signalling molecules. One of the best examples is apoptosis, the major mechanism used by eukaryotes to remove superfluous, damaged and potentially dangerous cells, in which a number of proteases have been found to play a central role. Of these the caspases have been considered to be the major players. However, more recently, other proteases have been increasingly suggested as being important in apoptosis, in particular the cysteine cathepsins. In this review the roles of caspases and cysteine cathepsins in apoptosis signalling are compared and discussed.

Abbreviations: BH3, Bcl-2 homology region 3, Bid, BH3-interacting domain death agonist, CARD, caspase recruitment domain, DED, death effector domain, DISC, death-inducing signalling complex, IAP, inhibitor of apoptosis protein, TNF, tumor necrosis factor

Keywords: Apoptosis, Caspases, Cathepsins, Cell death, Necrosis, Protease signalling