Fig. 1.

Diagrams showing the key components of the cell-based screening assays (hFas-W5 and hFas-W6) and two control assays (hFas-WT and hFas-P1-6). (A) hFas-W5 and hFas-W6 are designed to observe the effects of compounds on the signaling of individual RANK TRAF-binding motifs. (B) hFas-WT and hFas-P1-6 were used to determine maximum and minimum signaling activation for a given assay configuration. α-Fas induces an oligomerization of the chimeric receptor that fully activates the signaling of motifs that are not mutated. This leads to an increase in NF-κB translocation to the nucleus, and, as a consequence, an increase in luciferase gene activation. α-Fas, anti-human Fas activating antibody; hFas, human Fas; Luc, luciferase; NF-κB-RE, nuclear factor-kappa B responsive element; RANK, receptor activator of nuclear factor-kappa B; TRAF, TNFR associated factors.