Background on apoptosis Cell death can be achieved by two fundamentally different mechanisms, apoptosis and necrosis. Apoptosis is characterized by several morphological features that include condensation of nuclei and internucleosomal degradation of DNA, cell membrane blebbing, and formation of apoptotic bodies. By contrast, necrosis is recognized by swelling of the cell and organelles, follow...

Ubiquitin-mediated inactivation of caspases has long been postulated to contribute to the regulation of apoptosis. However, detailed mechanisms and functional consequences of caspase ubiquitylation have not been demonstrated. Here we show that the Drosophila Inhibitor of Apoptosis 1, DIAP1, blocks effector caspases by targeting them for polyubiquitylation and nonproteasomal inactivation. We dem...

Pyroptosis is a type of acute cell death that mainly occurs in immune cells. It characterized with robust release inflammatory cytokines and has emerged to play critical role the pathogenesis sepsis-associated disorders. In this study, we screened for pyroptotic inhibitors ultimate goal benefit sepsis treatments. Accidentally, identified nitrosonisoldipine (NTS), photodegradation product calciu...

Active caspases are generally composed of two catalytic domains, each containing a large (p20) and a small (p10) subunit so that a fully active caspase has the organization (p20-p10)(2). The cowpox serpin crmA suppresses host apoptosis and inflammation by inhibiting endogenous caspases. We report on the mechanism crmA uses to inhibit caspases 1, 6, and 8. Native PAGE showed formation of tight c...

Synthetic retinoid-related molecules (RRMs) have been described that show strong antiproliferative activity and induce apoptosis in cancer cells. These RRMs induce caspase activity independently of the retinoid receptors in Jurkat T cells. We observed that the inhibitor of cathepsins B and L Z-FA-fmk blocks the induction of DEVDase activity, DNA fragmentation, and externalization of phosphatidy...

The proteolytic activity of the cysteinyl aspartate-specific proteases, named caspases, mainly connotes their central role in apoptosis and inflammation. In this review we report on recent data on the role of caspases in the activation of nuclear factor kappaB (NF-kappaB), a transcription factor that fulfils a central role in innate and adaptive immunity, in cellular stress responses and in the...

The development of small molecules to modulate caspase activity offers a novel therapeutic strategy in the treatment of apoptosis-related and inflammatory diseases. Caspases are key mediators of apoptosis and inflammation; deregulation of their activation or expression can lead to the development of conditions such as neurodegenerative and autoinflammatory disorders. This review details the dif...

One function ascribed to apoptosis is the suicidal destruction of potentially harmful cells, such as cancerous cells. Hence, their growth depends on evasion of apoptosis, which is considered as one of the hallmarks of cancer. Apoptosis is ultimately carried out by the sequential activation of initiator and executioner caspases, which constitute a family of intracellular proteases involved in di...