Production of amyloid-beta-peptide by cultured cells: no evidence for internal initiation of translation at Met596.
It has been suggested that the A beta fragment of the amyloid precursor protein in Alzheimer's disease arises from internal translation initiation at Met596 (1). Here we use the recently described in vitro model of A beta production and secretion (2) to examine this hypothesis. We show that A beta is no longer detectable when the beta APP reading frame is destroyed by introduction of frame shift mutations that leave the A beta coding region intact. This result strongly suggests that internal initiation at Met596 does not contribute significantly to the amount of A beta observed.
Citron
M
M
Department of Neurology, Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02115.
Haass
C
C
Selkoe
D J
DJ
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D001483:Base Sequence; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000378:metabolism; D016368:Frameshift Mutation; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008715:Methionine / Q000378:metabolism*; D008969:Molecular Sequence Data; D010442:Peptide Chain Initiation, Translational; D016364:Reading Frames
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D018076:DNA, Complementary; D008715:Methionine