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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2000-12-28
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pubmed:abstractText |
Sequential proteolytic processing of the Amyloid Precursor Protein (APP) by beta- and gamma-secretases generates the 4-kDa amyloid (A beta) peptide, a key component of the amyloid plaques seen in Alzheimer's disease (AD). We and others have recently reported the identification and characterisation of an aspartic proteinase, Asp2 (BACE), as beta-secretase. Here we describe the characterization of a second highly related aspartic proteinase, Asp1 as a second beta-secretase candidate. Asp1 is expressed in brain as detected at the mRNA level and at the protein level. Transient expression of Asp1 in APP-expressing cells results in an increase in the level of beta-secretase-derived soluble APP and the corresponding carboxy-terminal fragment. Paradoxically there is a decrease in the level of soluble A beta secreted from the cells. Asp1 colocalizes with APP in the Golgi/endoplasmic reticulum compartments of cultured cells. Asp1, when expressed as an Fc fusion protein (Asp1-Fc), has the N-terminal sequence ALEP..., indicating that it has lost the prodomain. Asp1-Fc exhibits beta-secretase activity by cleaving both wild-type and Swedish variant (KM/NL) APP peptides at the beta-secretase site.
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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/Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1044-7431
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pubmed:author |
pubmed-author:ChapmanCC,
pubmed-author:ChapmanG AGA,
pubmed-author:ChristieGG,
pubmed-author:DingwallCC,
pubmed-author:GilmourLL,
pubmed-author:HowlettD RDR,
pubmed-author:HussainII,
pubmed-author:MeekT DTD,
pubmed-author:MurdockP RPR,
pubmed-author:PowellD JDJ,
pubmed-author:RatcliffeS JSJ,
pubmed-author:RyanD MDM,
pubmed-author:SchneiderKK,
pubmed-author:SimmonsD LDL,
pubmed-author:SouthanCC,
pubmed-author:TattersallDD,
pubmed-author:TestaT TTT,
pubmed-author:UHLD PDP,
pubmed-author:WalshF SFS
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pubmed:copyrightInfo |
Copyright 2000 Academic Press.
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pubmed:issnType |
Print
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
609-19
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11083922-Amyloid Precursor Protein Secretases,
pubmed-meshheading:11083922-Amyloid beta-Protein Precursor,
pubmed-meshheading:11083922-Animals,
pubmed-meshheading:11083922-Aspartic Acid Endopeptidases,
pubmed-meshheading:11083922-Binding Sites,
pubmed-meshheading:11083922-COS Cells,
pubmed-meshheading:11083922-Cloning, Molecular,
pubmed-meshheading:11083922-Endopeptidases,
pubmed-meshheading:11083922-Female,
pubmed-meshheading:11083922-Glycoproteins,
pubmed-meshheading:11083922-Humans,
pubmed-meshheading:11083922-Male,
pubmed-meshheading:11083922-Membrane Proteins,
pubmed-meshheading:11083922-Molecular Sequence Data,
pubmed-meshheading:11083922-Rabbits,
pubmed-meshheading:11083922-Recombinant Proteins,
pubmed-meshheading:11083922-Sequence Homology, Amino Acid
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pubmed:year |
2000
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pubmed:articleTitle |
ASP1 (BACE2) cleaves the amyloid precursor protein at the beta-secretase site.
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pubmed:affiliation |
Department of Neuroscience Research, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow. Essex, United Kingdom.
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pubmed:publicationType |
Journal Article
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