Perforin–granzyme–Fas ligand apoptotic pathway

The perforin–granzyme–Fas ligand apoptotic pathway comprises the primary cytotoxic mechanisms used by activated cytotoxic T lymphocytes (CTLs) and NKT(-like) lymphocytes to induce apoptosis of target cells. These mechanisms include the granule exocytosis pathway, in which perforin, a pore-forming protein, facilitates the entry of serine proteases called granzymes (particularly granzyme B) into target cell cytosol, thereby cleaving key substrates to activate apoptotic cascades, including direct caspase activation and mitochondrial disruption. Separately, Fas ligand (FasL) on T/NKT cells binds to Fas receptor on target cells, triggering the formation of the death-inducing signaling complex (DISC) and activation of caspases. Both routes converge on apoptotic executioner mechanisms to eliminate virus-infected, tumor, or otherwise dangerous cells. The pathway does not represent a single molecular target but rather a convergence of several effector mechanisms characteristic of cytotoxic lymphocytes.

Other names

Perforin/granzyme pathwayGranule exocytosis pathwayDeath receptor pathwayFas ligand pathwayCTL/NK cell cytotoxicity mechanisms

Induction of apoptosis via: - Perforin-dependent delivery of granzymes into target cells - Fas ligand–Fas receptor interaction triggering caspase activation