Distinct intramembrane cleavage of the beta-amyloid precursor protein family resembling gamma-secretase-like cleavage of Notch.
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.
Gu
Y
Y
Department of Neuropathology, Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Misonou
H
H
Sato
T
T
Dohmae
N
N
Takio
K
K
Ihara
Y
Y
D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D010450:Endopeptidases / Q000378:metabolism*; D006868:Hydrolysis; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D051880:Receptors, Notch
D016564:Amyloid beta-Protein Precursor; C437330:CTFgamma protein, rat; D008565:Membrane Proteins; D010446:Peptide Fragments; D051880:Receptors, Notch; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases