Apoptosis: mechanisms and relevance in cancer.
Apoptosis or programmed cell death is a process with typical morphological characteristics including plasma membrane blebbing, cell shrinkage, chromatin condensation and fragmentation. A family of cystein-dependent aspartate-directed proteases, called caspases, is responsible for the proteolytic cleavage of cellular proteins leading to the characteristic apoptotic features, e.g. cleavage of caspase-activated DNase resulting in internucleosomal DNA fragmentation. Currently, two pathways for activating caspases have been studied in detail. One starts with ligation of a death ligand to its transmembrane death receptor, followed by recruitment and activation of caspases in the death-inducing signalling complex. The second pathway involves the participation of mitochondria, which release caspase-activating proteins into the cytosol, thereby forming the apoptosome where caspases will bind and become activated. In addition, two other apoptotic pathways are emerging: endoplasmic reticulum stress-induced apoptosis and caspase-independent apoptosis. Naturally occurring cell death plays a critical role in many normal processes like foetal development and tissue homeostasis. Dysregulation of apoptosis contributes to many diseases, including cancer. On the other hand, apoptosis-regulating proteins also provide targets for drug discovery and new approaches to the treatment of cancer.
Vermeulen
Katrien
K
Faculty of Medicine, Laboratory of Experimental Hematology, Antwerp University Hospital, University of Antwerp, Wilrijkstraat 10, 2650, Edegem, Belgium.
Van Bockstaele
Dirk R
DR
Berneman
Zwi N
ZN
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D020169:Caspases / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly / Q000502:physiology; D053938:DNA Fragmentation / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D047109:Fetal Development / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism* / Q000628:therapy; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D019014:fas Receptor / Q000378:metabolism
D047888:Receptors, Tumor Necrosis Factor, Type I; D019014:fas Receptor; D020169:Caspases