Fas Receptor - Role in Apoptosis

Role in Apoptosis

Some reports have suggested that the extrinsic Fas pathway is sufficient to induce complete apoptosis in certain cell types through DISC assembly and subsequent caspase-8 activation.

These cells are dubbed Type 1 cells and are characterized by the inability of anti-apoptotic members of the Bcl-2 family (namely Bcl-2 and Bcl-xL) to protect from Fas-mediated apoptosis.

Characterized Type 1 cells include H9, CH1, SKW6.4 and SW480, all of which are lymphocyte lineages except the latter, which is a colon adenocarcinoma lineage.

However, evidence for crosstalk between the extrinsic and intrinsic pathways exists in the Fas signal cascade.

In most cell types, caspase-8 catalyzes the cleavage of the pro-apoptotic BH3-only protein Bid into its truncated form, tBid. BH-3 only members of the Bcl-2 family exclusively engage anti-apoptotic members of the family (Bcl-2, Bcl-xL), allowing Bak and Bax to translocate to the outer mitochondrial membrane, thus permeabilizing it and facilitating release of pro-apoptotic proteins such as cytochrome c and Smac/DIABLO, an antagonist of inhibitors of apoptosis proteins (IAPs).