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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2000-2-17
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pubmed:abstractText |
The Alzheimer's disease beta-amyloid peptide (Abeta) is produced by excision from the type 1 integral membrane glycoprotein amyloid precursor protein (APP) by the sequential actions of beta- and then gamma-secretases. Here we report that Asp 2, a novel transmembrane aspartic protease, has the key activities expected of beta-secretase. Transient expression of Asp 2 in cells expressing APP causes an increase in the secretion of the N-terminal fragment of APP and an increase in the cell-associated C-terminal beta-secretase APP fragment. Mutation of either of the putative catalytic aspartyl residues in Asp 2 abrogates the production of the fragments characteristic of cleavage at the beta-secretase site. The enzyme is present in normal and Alzheimer's disease (AD) brain and is also found in cell lines known to produce Abeta. Asp 2 localizes to the Golgi/endoplasmic reticulum in transfected cells and shows clear colocalization with APP in cells stably expressing the 751-amino-acid isoform of APP.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid Precursor Protein Secretases,
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Protein Precursor,
http://linkedlifedata.com/resource/pubmed/chemical/Aspartic Acid Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/BACE1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/BACE2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cathepsin D,
http://linkedlifedata.com/resource/pubmed/chemical/Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Papain,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1044-7431
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pubmed:author |
pubmed-author:ChapmanCC,
pubmed-author:ChristieGG,
pubmed-author:DingwallCC,
pubmed-author:GlogerI SIS,
pubmed-author:HowlettD RDR,
pubmed-author:HussainII,
pubmed-author:MeekT DTD,
pubmed-author:MurphyK EKE,
pubmed-author:PowellDD,
pubmed-author:RyanD MDM,
pubmed-author:SimmonsD LDL,
pubmed-author:SmithT STS,
pubmed-author:SouthanC DCD,
pubmed-author:UHLD PDP,
pubmed-author:WalshF SFS
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pubmed:issnType |
Print
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pubmed:volume |
14
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
419-27
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pubmed:dateRevised |
2010-8-25
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pubmed:meshHeading |
pubmed-meshheading:10656250-Alzheimer Disease,
pubmed-meshheading:10656250-Amino Acid Sequence,
pubmed-meshheading:10656250-Amino Acid Substitution,
pubmed-meshheading:10656250-Amyloid Precursor Protein Secretases,
pubmed-meshheading:10656250-Amyloid beta-Protein Precursor,
pubmed-meshheading:10656250-Animals,
pubmed-meshheading:10656250-Aspartic Acid Endopeptidases,
pubmed-meshheading:10656250-COS Cells,
pubmed-meshheading:10656250-Cathepsin D,
pubmed-meshheading:10656250-Cell Line,
pubmed-meshheading:10656250-Cell Membrane,
pubmed-meshheading:10656250-Endopeptidases,
pubmed-meshheading:10656250-Female,
pubmed-meshheading:10656250-Hippocampus,
pubmed-meshheading:10656250-Humans,
pubmed-meshheading:10656250-Middle Aged,
pubmed-meshheading:10656250-Molecular Sequence Data,
pubmed-meshheading:10656250-Mutagenesis, Site-Directed,
pubmed-meshheading:10656250-Papain,
pubmed-meshheading:10656250-Recombinant Proteins,
pubmed-meshheading:10656250-Sequence Alignment,
pubmed-meshheading:10656250-Sequence Homology, Amino Acid,
pubmed-meshheading:10656250-Transfection
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pubmed:year |
1999
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pubmed:articleTitle |
Identification of a novel aspartic protease (Asp 2) as beta-secretase.
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pubmed:affiliation |
Department of Neurosciences, SmithKline Beecham Pharmaceuticals, Harlow, Essex, United Kingdom.
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pubmed:publicationType |
Journal Article
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