Fas-induced apoptosis, and diseases caused by its abnormality

Homeostasis of multicellular organisms is controlled not only by proliferation and differentiation of cells but also by cell death. Physiological cell death mostly proceeds by apoptosis, a process which includes condensation and segmentation of the nuclei and cytoplasm, and often extensive fragmentation of chromosomal DNA into nucleosome units. Molecular and cellular characterization of Fas, a cell-surface protein recognized by cytotoxic monoclonal antibodies, has led to its definition as a receptor for a Fas ligand (Fast). Fast binds to Fas, which results in target cell apoptosis. A family of cysteine proteases seems to be sequentially activated during the Fas-mediated apoptosis. The phenotypes of the loss-of-function mutants of Fas and Fast indicate that this system is involved in T cell-mediated cytotoxicity, in down-regulation of immune responses, and probably in the turnover of senescent cells. Malfunction of the Fas system causes hyperplasia in peripheral lymphoid organs and the liver, accelerating autoimmune diseases and tumorigenesis, whereas exaggeration of the system leads to tissue disruption.