Gamma-Secretase Activating Protein (gSAP)

Formation of amyloid-beta is catalyzed by gamma-secretase, a protease with numerous substrates. PION, or GSAP, selectively increases amyloid-beta production through a mechanism involving its interaction with both gamma-secretase and its substrate, the amyloid-beta precursor protein (APP) C-terminal fragment (APP-CTF) . The predicted full-length human GSAP protein contains 854 amino acids. Its sequence, particularly the C-terminal region, is highly conserved from chicken to human. Real-time PCR detected Gsap expression in diverse mouse tissues, with highest levels in lung, kidney, liver, and brain. Pulse-chain analysis of mouse N2a neuroblastoma cells showed that endogenous Gsap was synthesized as a 98-kD holoprotein that was rapidly processed into a 16-kD C-terminal fragment.