Two-way cleavage of beta-amyloid protein precursor by multicatalytic proteinase.
The beta-amyloid protein (beta-AP) derived from a beta-amyloid protein precursor (APP) is a hallmark of Alzheimer's disease. The abundant generation of beta-AP suggests the abnormal processing of APP, but the molecular mechanism remains unclear. The main APP-processing enzyme was purified from the rat brain and identified to be a macropain-like multicatalytic proteinase. The purified enzyme cleaved the Gln15-Lys16 bond of beta-AP, but altered to cleave at the N-terminus of beta-AP to release the extracellular domain of beta-AP in the presence of Ca2+. These findings suggest that the functional change in this multicatalytic proteinase may result in abnormal processing of APP.
Kojima
S
S
Research Institute, Sumitomo Pharmaceuticals Co., Osaka, Japan.
Omori
M
M
D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002850:Chromatography, Gel; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008670:Metals / Q000494:pharmacology; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D051381:Rats; D016415:Sequence Alignment
D016564:Amyloid beta-Protein Precursor; D008670:Metals; D009097:Multienzyme Complexes; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex