[Caspases and apoptosis: die and let live].
Apoptosis (genetically programmed cell death) plays a key role in human physiology and pathogenesis of various diseases, including cancer. A suicide of cell can be initiated by many different factors, but activation of caspases, which are a special class of proteolytic enzymes, is always involved in this process. Activation of caspases may be achieved by several molecular pathways: the best known stimuli triggering caspase cascade are stimulation of Fas or TNF receptors, release of cytochrome c from the cellular mitochondria and exposure to granzymes, which are secreted by cytotoxic T cells. Activated caspases digest many cellular proteins responsible for cell cycle regulation (e.g. RB, MDM2), DNA damage recognition and repair (e.g. DNA-PK, P53, PARP), and regulation of the cellular structure (e.g. actin and lamins). All these functional and structural protein modifications lead directly to apoptosis. Further research on the mechanisms controlling caspase activity and the modes of action will provide better insight into pathogenesis of cancer and other disorders. It may be even the first step to design new and more efficient methods of conventional tumor treatment or gene therapy.
Nalepa
Grzegorz
G
Katedry i Kliniki Chorób Wewnetrznych, Diabetologii i Nefrologii w Zabrzu.
Zukowska-Szczechowska
Ewa
E
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D003574:Cytochrome c Group / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D019014:fas Receptor / Q000378:metabolism
D003574:Cytochrome c Group; D019014:fas Receptor; D020169:Caspases