Amyloid Precursor Protein Processing in Sterol Regulatory Element-binding Protein Site 2 Protease-deficient Chinese Hamster Ovary Cells

Amyloid peptides of 39–43 amino acids (Aβ) are the major constituents of amyloid plaques present in the brains of Alzheimer’s (AD) patients. Proteolytic processing of the amyloid precursor protein (APP) by the yet unidentified β- and γ-secretases leads to the generation of the amyloidogenic A...

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Bibliographic Details
Published in:The Journal of biological chemistry 1998-06, Vol.273 (25), p.15309-15312
Main Authors: Ross, S L, Martin, F, Simonet, L, Jacobsen, F, Deshpande, R, Vassar, R, Bennett, B, Luo, Y, Wooden, S, Hu, S, Citron, M, Burgess, T L
Format: Article
Language:English
Subjects:
Amyloid beta-Peptides - metabolism
Amyloid beta-Protein Precursor - metabolism
Amyloid Precursor Protein Secretases
Animals
Aspartic Acid Endopeptidases
CHO Cells
Clone Cells
Cricetinae
Endopeptidases - deficiency
Endopeptidases - genetics
Endopeptidases - metabolism
Endopeptidases - physiology
Humans
Peptide Fragments - metabolism
RNA, Messenger - metabolism
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Summary:Amyloid peptides of 39–43 amino acids (Aβ) are the major constituents of amyloid plaques present in the brains of Alzheimer’s (AD) patients. Proteolytic processing of the amyloid precursor protein (APP) by the yet unidentified β- and γ-secretases leads to the generation of the amyloidogenic Aβ peptides. Recent data suggest that all of the known mutations leading to early onset familial AD alter the processing of APP such that increased amounts of the 42-amino acid form of Aβ are generated by a γ-secretase activity. Identification of the β- and/or γ-secretases is a major goal of current AD research, as they are prime targets for therapeutic intervention in AD. It has been suggested that the sterol regulatory element-binding protein site 2 protease (S2P) may be identical to the long sought γ-secretase. We have directly tested this hypothesis using over-expression of the S2P cDNA in cells expressing APP and by characterizing APP processing in mutant Chinese hamster ovary cells that are deficient in S2P activity and expression. The data demonstrate that S2P does not play an essential role in the generation or secretion of Aβ peptides from cells, thus it is unlikely to be a γ-secretase.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.273.25.15309