Source:http://linkedlifedata.com/resource/pubmed/id/10575009
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
49
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| pubmed:dateCreated |
2000-2-3
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| pubmed:abstractText |
Mutant presenilins (PS) contribute to the pathogenesis of familial Alzheimer's disease (FAD) by enhancing the production of Abeta42 from beta-amyloid precursor protein. Presenilins are endoproteolytically processed to N-terminal and C-terminal fragments, which together form a stable 1:1 complex. We have mapped the cleavage site in the PS2 protein by direct sequencing of its C-terminal fragment isolated from mouse liver. Three different N-terminal residues were identified starting at Val-299, Thr-301, and Leu-307 that correspond closely to the previously described N termini of the C-terminal fragment of human PS1. Mutational analysis of the PS2 cleavage site indicates that the principal endoproteolytic cleavage occurs at residues Met-298/Val-299 and that the N terminus is subsequently modified by secondary proteolytic cleavages. We have generated cleavage defective PS2 constructs, which accumulate exclusively as full-length polypeptides in transfected Neuro2a cells. Functional analysis of such cleavage defective PS2 carrying the FAD mutation Asn-141 --> Ile showed that its Abeta42 producing activity was strongly reduced compared with cleavage-competent FAD PS2. In contrast, cleavage defective PS2 was active in rescuing the egg-laying defect of a sel-12 mutant in Caenorhabditis elegans. We conclude that PS2 endoproteolytic cleavage is not an absolute requirement for its activities but may rather selectively enhance or stabilize its functions.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PSEN2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Presenilin-2,
http://linkedlifedata.com/resource/pubmed/chemical/amyloid beta-protein (1-42)
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
3
|
| pubmed:volume |
274
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
35233-9
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:10575009-Alzheimer Disease,
pubmed-meshheading:10575009-Amino Acid Sequence,
pubmed-meshheading:10575009-Amyloid beta-Peptides,
pubmed-meshheading:10575009-Animals,
pubmed-meshheading:10575009-Animals, Genetically Modified,
pubmed-meshheading:10575009-Caenorhabditis elegans,
pubmed-meshheading:10575009-Cells, Cultured,
pubmed-meshheading:10575009-Humans,
pubmed-meshheading:10575009-Membrane Proteins,
pubmed-meshheading:10575009-Mice,
pubmed-meshheading:10575009-Molecular Sequence Data,
pubmed-meshheading:10575009-Mutagenesis, Insertional,
pubmed-meshheading:10575009-Mutagenesis, Site-Directed,
pubmed-meshheading:10575009-Peptide Fragments,
pubmed-meshheading:10575009-Precipitin Tests,
pubmed-meshheading:10575009-Presenilin-2,
pubmed-meshheading:10575009-Promoter Regions, Genetic,
pubmed-meshheading:10575009-Sequence Homology, Amino Acid,
pubmed-meshheading:10575009-Tissue Distribution,
pubmed-meshheading:10575009-Transfection
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| pubmed:year |
1999
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| pubmed:articleTitle |
The influence of endoproteolytic processing of familial Alzheimer's disease presenilin 2 on abeta42 amyloid peptide formation.
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| pubmed:affiliation |
Pharma Division, Preclinical Central Nervous System Research, CH-4070 Basel, Switzerland. helmut.jacobsen@roche.com
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| pubmed:publicationType |
Journal Article
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