Alpha- and beta- cleavages of the amino-terminus of the cellular prion protein.
It is commonly assumed that the physiological isoform of prion protein, PrP(C), is cleaved during its normal processing between residues 111/112, whereas the pathogenic isoform, PrP(Sc), is cleaved at an alternate site in the octapeptide repeat region around position 90. Here we demonstrated both in cultured cells and in vivo, that PrP(C) is subject to a complex set of post-translational processing with the molecule being cleaved upstream of position 111/112, in the octapeptide repeat region or at position 96. PrP has therefore two main cleavage sites that we decided to name alpha and beta. Cleavage of PrP(C) at these sites leads us to re-evaluate the function of both N- and C-terminus fragments thus generated.
Mangé
Alain
A
Institut de Génétique Humaine, CNRS U.P.R. 1142, 141, rue de la Cardonille, 34396 Montpellier Cedex 5, France.
Béranger
Florence
F
Peoc'h
Katell
K
Onodera
Takashi
T
Frobert
Yveline
Y
Lehmann
Sylvain
S
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D006224:Cricetinae; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D018621:PrPC Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D017384:Sequence Deletion / Q000235:genetics; D014162:Transfection
D010446:Peptide Fragments; D018621:PrPC Proteins