Protease cascade

Fig. 2. A possible protease cascade mechanism for extracellular degradation and metastasis. Active proteases are shown in boxes with dark background, while inhibitors are shown in boxes with light background. Reproduced with permission from Schmitt et al.. Fibrinolysis, copyright 1992...

Wang, X., 1997, Cytochrome c and dATP-dependent formation of Apaf-l/caspase-9 complex initiates an apoptotic protease cascade. Cell 91 479-489. 

Li, P., Nijhawan, D., Budihardjo, 1., Srinivasula, S.M., Ahmad, M., Alnemri, E.S., and Wang, X,. 1997, Cytochrome c and dATP-dependent formation of Apaf-l/caspase-9 complex initiates an apoptotic protease cascade. Cell 91 479-489. 

An essential part of the apoptotic program is a caspase cascade. Apoptosis is initiated by proteolytic processing of intiator-procapsases under the influence of a variety of signals. The mature initiator caspase catalyzes the processing of a effector-procaspase to the active enzyme, which degrades specific substrates and/or activates further procaspases. In this way, caspases can be activated sequentially in a protease cascade. 

Similar to the MAP kinase cascades for protein phosphorylation, protease cascades exist, in which downstream proteases are activated by the action of upstream proteases (3). One of the most famous cascades is the caspase cascade that leads to apoptosis (Fig. 22) (11, 136). Caspases are Cys proteases that cleave the amide bond specifically after an Asp residue. Two types of caspases exist, initiator caspases (Caspase 2, 8, 9, 10) and effector caspases (Caspase 3, 6, 7). Both initiator and effector... 

Death receptors are involved in signaling of programmed cell death (apoptosis). CD95 (Example 6.4) is a member of the death receptor family. Binding of specific ligands to death receptors leads to their trimerization. This triggers activation of an intracellular protease cascade. These proteases (the caspases) cleave many intracellular proteins, leading to cell death. 

The present studies show that camosic acid, camosol, and ursolic acid induced apoptosis in HL-60 cells in a concentration- and time-dependent manner. Rosmarinic acid did not interfere HL-60 cell viability. We also showed that camosic acid, camosol, or ursolic acid activated caspase-3 and -9, and caused cleavage and degradation of down stream death substrates PARP and DFF45/ICAD. These results indicate that the typical death protease cascade mediates camosic acid-, camosol-, or ursolic acid-induced apoptosis in HL-60 cells. 

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