Fas cell surface death receptor and Fas ligand (FAS/FASL)

The Fas (CD95) receptor and its cognate Fas ligand (FasL/CD178) are central mediators of the extrinsic apoptotic pathway, playing a vital role in maintaining immune homeostasis and eliminating infected or malignant cells. Fas is a type I transmembrane death receptor that, upon binding to the homotrimeric FasL, recruits adapter proteins like FADD to form the Death-Inducing Signaling Complex (DISC), which activates the caspase cascade leading to programmed cell death. Beyond apoptosis, the system also influences non-apoptotic pathways such as NF-κB and MAPK signaling, contributing to inflammation and cell proliferation. In oncology, tumors often exploit this pathway by overexpressing FasL to induce apoptosis in infiltrating lymphocytes (the "Fas counterattack") or by downregulating Fas to evade immune surveillance. Therapeutic interventions include the use of fusion proteins like Asunercept to block the Fas/FasL interaction in conditions like myelodysplastic syndromes and glioblastoma, where excessive apoptosis or immune evasion drives disease progression. However, systemic activation of the Fas receptor remains a significant clinical challenge due to the high risk of lethal hepatotoxicity caused by massive liver cell death.

Other names

CD95APO-1TNFRSF6TNFSF6CD178FASLGAPT1FasRFasLApoptosis antigen 1

Inhibition of the Fas/FasL interaction to prevent pathological apoptosis or activation of the Fas receptor to induce apoptosis in target cells.