Abstract
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.
MeSH terms
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Amyloid Precursor Protein Secretases
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Amyloid beta-Peptides / biosynthesis*
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Amyloid beta-Protein Precursor / biosynthesis
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Amyloid beta-Protein Precursor / metabolism
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Animals
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Aspartic Acid Endopeptidases
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Biological Transport
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CCAAT-Enhancer-Binding Proteins*
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CHO Cells
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Cricetinae
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DNA-Binding Proteins / metabolism*
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Endopeptidases / metabolism
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Glycosylation
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Humans
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Mutation
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Nuclear Proteins / metabolism*
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Protein Processing, Post-Translational
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Sterol Regulatory Element Binding Protein 1
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Transcription Factors*
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Transfection
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Tyrosine / metabolism
Substances
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Amyloid beta-Peptides
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Amyloid beta-Protein Precursor
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CCAAT-Enhancer-Binding Proteins
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DNA-Binding Proteins
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Nuclear Proteins
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SREBF1 protein, human
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Sterol Regulatory Element Binding Protein 1
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Transcription Factors
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Tyrosine
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Amyloid Precursor Protein Secretases
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Endopeptidases
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Aspartic Acid Endopeptidases
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BACE1 protein, human