Proteasome-Mediated Degradation of the C-terminus of the Alzheimer's Disease β-Amyloid Protein Precursor: Effect of C-Terminal Truncation on Production of β-Amyloid Protein

Abstract

The β-amyloid protein (Aβ) is derived by proteolytic processing of the amyloid protein precursor (APP). Cleavage of APP by β-secretase generates a C-terminal fragment (APP-CTFβ), which is subsequently cleaved by γ-secretase to produce Aβ. Our previous studies have shown that the proteasome can cleave the C-terminal cytoplasmic domain of APP. To identify proteasome cleavage sites in APP, two peptides homologous to the C-terminus of APP were incubated with recombinant 20S proteasome. Cleavage of the peptides was monitored by reversed phase high-performance liquid chromatography and mass spectrometry. Proteasome cleaved the APP C-terminal peptides at several sites, including a region around the..