Lack of beta-amyloid production in M19 cells deficient in site 2 processing of the sterol regulatory element binding proteins.
The processing of the amyloid precursor protein (APP) and the sterol regulatory element binding protein show remarkable analogies. Following a first lumenal cleavage, both proteins undergo a cleavage within the transmembrane domain by enzymatic activities named gamma-secretase and S2P, respectively. We analyzed the processing of APP in the mutant Chinese hamster ovary (CHO) cell line M19 which lacks the S2P gene encoding for a putative metalloprotease. In these cells, we were not able to detect any beta-amyloid production from endogenous or transiently overexpressed APP, although the transport of APP along the secretory pathway, its processing by alpha- and beta-secretase, as well as its secretion were normal. This strongly suggests that the gamma-secretase cleavage in M19 cells is severely impaired.
Manni
M E
ME
Novartis Pharma Ltd., Basel, Switzerland.
Cescato
R
R
Paganetti
P A
PA
D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D001692:Biological Transport; D022762:CCAAT-Enhancer-Binding Proteins; D016466:CHO Cells; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D014443:Tyrosine; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human