Biology Reference
In-Depth Information
Fig. 9. Proposed steps of apoptosis induced by Fas ligand.
receptor trimerization. Activated receptors recruit adaptor molecules such as Fas-associating protein
with death domain (FADD), which recruit procaspase 8 to the receptor complex where it undergoes
autocatalytic activation. Activated caspase 8 activates caspase 3 through two pathways; the complex
one is that caspase 8 cleaves Bcl-2 interacting protein (Bid) and its COOH-terminal part translocates
to mitochondria where it triggers cytochrome c release. The released cytochrome c binds to apoplectic
protease activating factor-1 (Apaf-1) together with dATP and procaspase 9 and activates caspase 9. The
caspase 9 cleaves procaspase 3 and activates caspase 3. The other pathway is that caspase 8 cleaves
procaspase3 directly and activates it. The caspase 3 cleaves DNA fragmentation factor (DFF) 45 in a
heterodimeric factor of DFF40 and DFF45. Cleaved DFF45 dissociates from DFF40, inducing oligomer-
ization of DFF40 that has DNase activity. The active DFF40 oligomer causes the internucleosomal DNA
fragmentation, which is an apoptotic hallmark indicative of chromatin condensation.
We generated an HFPN model for this mechanism with GON. The pathways consist of several
