Induction of Apoptosis

Apoptosis in T cells and other cells can be activated through cell surface receptors called FAS,Fas are member of TNF receptor family and binds to TNF family member. FasL (FAS ligand) expressed on the surface of other cells, usually activated T cells.

FASL ligands like other TNF family members are a trimmer, and when FAS receptors bind trimmer ligands, three receptors chains are brought together to form a other trimmer.Bringing together the intercellular domains of Fas, which contains adapter molecules called death domains, allows them to bind other intercellular death domains containing protein such as FADD.

A FADD act has an adapter linking FAS to caspase 8;a member of intercellular protease called Caspases.It cleaves at the C terminal side of the aspartic acid residues.Initially Caspase 8 binds as a inactive precursor, but once bound pro-caspase molecule are able activate each other by cleavage and by second cleavage to release the protease domain from the complex proteins assembled around the Fas receptors.
Caspase 8 proteolytic domain activates other pro-caspases, which can in turn activates other pro-caspases in a proteolytc cascade.At the end of the cascade is a important effector caspase called caspase 3,which cleaves the protein called I-CAD the inhibitor of caspase activated DNA.By cleaving I-CAD inhibitor, the caspase3 releases active DNA, which is able to migrate to nucleus.In the nucleus the caspase activated DNA degrades chromatin, cutting the DNA into small pieces and ultimately killing the cell