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rdf:type |
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lifeskim:mentions |
umls-concept:C0026882,
umls-concept:C0085151,
umls-concept:C0299212,
umls-concept:C0596311,
umls-concept:C1235660,
umls-concept:C1330957,
umls-concept:C1418985,
umls-concept:C1515877,
umls-concept:C1552644,
umls-concept:C1823153,
umls-concept:C1879547,
umls-concept:C2349976
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pubmed:issue |
39
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pubmed:dateCreated |
2002-9-23
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pubmed:abstractText |
The presenilin 1 (PS1) and presenilin 2 (PS2) proteins are necessary for proteolytic cleavage of the amyloid precursor protein (APP) within its transmembrane domain. One of these cleavage events (termed gamma-secretase) generates the C-terminal end of the Abeta-peptide by proteolysis near residue 710 or 712 of APP(770). Another event (termed gamma-like or epsilon-secretase cleavage) cleaves near residue 721 at approximately 2-5 residues inside the cytoplasmic membrane boundary to generate a series of stable, C-terminal APP fragments. This latter cleavage is analogous to S3-cleavage of Notch. We report here that specific mutations in the N terminus, loop, or C terminus of PS1 all increase the production of Abeta(42) but cause inhibition of both epsilon-secretase cleavage of APP and S3-cleavage of Notch. These data support the hypothesis that epsilon-cleavage of APP and S3-cleavage of Notch are similar events. They also argue that, although both the gamma-site and the epsilon-site cleavage of APP are presenilin-dependent, they are likely to be independent catalytic events.
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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/Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PSEN1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Presenilin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Notch
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
27
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
36521-6
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12119298-Amino Acid Sequence,
pubmed-meshheading:12119298-Amyloid Precursor Protein Secretases,
pubmed-meshheading:12119298-Amyloid beta-Protein Precursor,
pubmed-meshheading:12119298-Aspartic Acid Endopeptidases,
pubmed-meshheading:12119298-Blotting, Western,
pubmed-meshheading:12119298-Catalysis,
pubmed-meshheading:12119298-Cell Line,
pubmed-meshheading:12119298-Endopeptidases,
pubmed-meshheading:12119298-Enzyme Activation,
pubmed-meshheading:12119298-Humans,
pubmed-meshheading:12119298-Mass Spectrometry,
pubmed-meshheading:12119298-Membrane Proteins,
pubmed-meshheading:12119298-Microsomes,
pubmed-meshheading:12119298-Models, Genetic,
pubmed-meshheading:12119298-Molecular Sequence Data,
pubmed-meshheading:12119298-Mutation,
pubmed-meshheading:12119298-Precipitin Tests,
pubmed-meshheading:12119298-Presenilin-1,
pubmed-meshheading:12119298-Protein Binding,
pubmed-meshheading:12119298-Protein Structure, Tertiary,
pubmed-meshheading:12119298-Receptors, Notch,
pubmed-meshheading:12119298-Temperature,
pubmed-meshheading:12119298-Transfection
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pubmed:year |
2002
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pubmed:articleTitle |
Presenilin 1 mutations activate gamma 42-secretase but reciprocally inhibit epsilon-secretase cleavage of amyloid precursor protein (APP) and S3-cleavage of notch.
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pubmed:affiliation |
Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, Toronto, Ontario M5S 3H2, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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