[Frontiers in Bioscience 14, 583-595, January 1, 2009]
1Weston Laboratory, Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Hospital Campus, London, UK, 2Basic Research Department, Epithelial Biomedicine Division, Molecular Oncology Unit, Ciemat, Madrid, Spain, 3Merck Research Laboratories, Rahway, USA
FIGURES
Figure 1. Apoptosis is induced by a subgroup of the tumor necrosis factor (TNF) receptor superfamily, the so called death receptors. Eight human death receptors are known to date. They are typically type I or type II transmembrane proteins that share a conserved 80 amino acid sequence, the death domain, in their cytoplasmic tail, and contain two to four cysteine rich extracellular domains that are involved in ligand binding. The known ligands for these receptors are denoted.
Figure 2. Fas/FasL-triggered apoptosis is the best characterised cell death receptor induced pathway. Upon Fas oligomerisation the adaptor molecule FADD and the pro-form of caspase 8 are sequentially recruited to the intracellular potion of the receptor via DD and DED interactions. The regulator c-FLIP can also be recruited to this complex named death-inducing signaling complex (DISC). The resulting oligomerisation of procaspase 8 results in its autoproteolytic processing and activation. The ensuing apoptotic program kills cells via two different pathways: either active caspase 8 directly cleaves and activates caspase 3 (type I) or caspase 3 cleavage is induced indirectly through cleavage of Bid and activation of the mitochondrial pathway (type II).