Atlas of Genetics and Cytogenetics in Oncology and Haematology The Fas- Fas Ligand apoptotic pathway

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, followed by disintegration of the cell and the release of cytoplasmic material. Although the necrotic signalling pathway remains largely uncharacterized at the molecular level, apoptosis is known to be dependent on a family of intracellular cysteine proteases, called CASPASES (Cysteine Aspartate Specific ProteASEs). Caspases (Nicholson DW, 1999) are initially synthesized as inactive cytosolic proteases (proenzymes) which have a p20 and a p10 domain that, in response to apoptotic stimulation, are cleaved to form the active enzyme. Active caspases then cleave other caspases, Bcl-2 family members, or act on various nuclear substrates, such as lamins and caspase-activated DNase (CAD), finally leading to apoptosis. Caspases contain a cysteine residue within th