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rdf:type |
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lifeskim:mentions |
umls-concept:C0006104,
umls-concept:C0013935,
umls-concept:C0017262,
umls-concept:C0025914,
umls-concept:C0026809,
umls-concept:C0026882,
umls-concept:C0086418,
umls-concept:C0185117,
umls-concept:C0302891,
umls-concept:C0392747,
umls-concept:C0425245,
umls-concept:C0439855,
umls-concept:C0443172,
umls-concept:C0450254,
umls-concept:C0547040,
umls-concept:C0596607,
umls-concept:C0872078,
umls-concept:C1260957,
umls-concept:C1704241,
umls-concept:C1880022,
umls-concept:C2911684
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pubmed:issue |
2
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pubmed:dateCreated |
2004-1-13
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pubmed:abstractText |
The presenilin proteins are required for intramembrane cleavage of a subset of type 1 membrane proteins including the Alzheimer's disease amyloid precursor protein. Previous studies indicate presenilin proteins form enzymatically active high molecular mass complexes consisting of heterodimers of N- and C-terminal fragments in association with nicastrin, presenilin enhancer-2 and anterior pharynx defective-1 proteins. Using Blue Native gel electrophoresis (BN/PAGE) we have studied endogenous presenilin 1 complex mass, stability and association with nicastrin, presenilin enhancer-2 and anterior pharynx defective-1. Solubilization of mouse or human brain membranes with dodecyl-d-maltoside produced a 360-kDa species reactive with antibodies to presenilin 1. Presenilin 1 complex levels were high in embryonic brain. Complex integrity was sensitive to Triton X-100 and SDS, but stable to reducing agent. Addition of 5 M urea caused complex dissolution and nicastrin to migrate as a subcomplex. Nicastrin and presenilin enhancer-2 were detected in the presenilin 1 complex following BN/PAGE, electroelution and second-dimension analysis. Anterior pharynx defective-1 was detected as an 18-kDa form and 9-kDa C-terminal fragment by standard SDS/PAGE of mouse tissues, and as a predominant 36-kDa band after presenilin 1 complex second-dimension analysis. Membranes from brain cortex of Alzheimer's disease patients, or from cases with presenilin 1 missense mutations, indicated no change in presenilin 1 complex mobility. Higher molecular mass presenilin 1-reactive species were detected in brain containing presenilin 1 exon 9 deletion mutation. This abnormality was confirmed using cells transfected with the same presenilin deletion mutation.
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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/APH1A protein, human,
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/Bace1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/CTNNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Catnb protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PSEN1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PSENEN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Presenilin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin,
http://linkedlifedata.com/resource/pubmed/chemical/nicastrin protein
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0014-2956
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
271
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
375-85
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:14717705-Alzheimer Disease,
pubmed-meshheading:14717705-Amyloid Precursor Protein Secretases,
pubmed-meshheading:14717705-Amyloid beta-Protein Precursor,
pubmed-meshheading:14717705-Animals,
pubmed-meshheading:14717705-Aspartic Acid Endopeptidases,
pubmed-meshheading:14717705-Brain,
pubmed-meshheading:14717705-Cell Membrane,
pubmed-meshheading:14717705-Cells, Cultured,
pubmed-meshheading:14717705-Cytoskeletal Proteins,
pubmed-meshheading:14717705-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:14717705-Endopeptidases,
pubmed-meshheading:14717705-Exons,
pubmed-meshheading:14717705-Humans,
pubmed-meshheading:14717705-Membrane Glycoproteins,
pubmed-meshheading:14717705-Membrane Proteins,
pubmed-meshheading:14717705-Mice,
pubmed-meshheading:14717705-Mutation, Missense,
pubmed-meshheading:14717705-Peptide Hydrolases,
pubmed-meshheading:14717705-Presenilin-1,
pubmed-meshheading:14717705-Sequence Deletion,
pubmed-meshheading:14717705-Trans-Activators,
pubmed-meshheading:14717705-beta Catenin
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pubmed:year |
2004
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pubmed:articleTitle |
Characterization of presenilin complexes from mouse and human brain using Blue Native gel electrophoresis reveals high expression in embryonic brain and minimal change in complex mobility with pathogenic presenilin mutations.
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pubmed:affiliation |
Department of Pathology, The University of Melbourne, Australia. janetta@unimelb.edu.au
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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