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J Biol Chem. 2001 Sep 21;276(38):35235-8. Epub 2001 Aug 1.

Distinct intramembrane cleavage of the beta-amyloid precursor protein family resembling gamma-secretase-like cleavage of Notch.

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  • 1Department of Neuropathology, Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.


The intramembrane cleavage of beta-amyloid precursor protein by gamma-secretase is the final step in the generation of amyloid beta-protein. A 59- or 57-residue C-terminal fragment called CTFgamma is produced concomitantly. Putative CTFgamma generated in rat brain membrane preparations was purified and sequenced. Instead of CTFgamma, shorter 50- and 49-residue fragments were identified. In addition, we found similar C-terminal fragments of beta-amyloid precursor-like proteins 1 and 2; these were also cleaved at corresponding sites. This newly identified cleavage occurs at a site two to five residues inside the cytoplasmic membrane boundary, which is very similar to gamma-secretase-like cleavage of Notch 1.

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