Figure 1. The principle of the γ-secretase epsilon-cleavage assay.

Upon cleavage of the C99 (or other γ-secretase substrates) hybrid protein by γ-secretase, the rTA is released from the membrane and enters nucleus to bind tetO DNA-binding site to stimulate luciferase reporter gene activity as measurement for total cleavage, both by endogenous and by transfected γ-secretase variants. (Xu et al., 2016)