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rdf:type |
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lifeskim:mentions |
umls-concept:C0004083,
umls-concept:C0007610,
umls-concept:C0040715,
umls-concept:C0085151,
umls-concept:C0175631,
umls-concept:C0439851,
umls-concept:C0599718,
umls-concept:C0599813,
umls-concept:C0599893,
umls-concept:C1412459,
umls-concept:C1514562,
umls-concept:C1522702,
umls-concept:C1552596,
umls-concept:C1552644,
umls-concept:C1823153,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221,
umls-concept:C1947931,
umls-concept:C2349976,
umls-concept:C2827662
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pubmed:issue |
4
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pubmed:dateCreated |
2002-10-2
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pubmed:abstractText |
Amyloid-beta, the peptide that deposits as senile plaques in Alzheimer's disease, is derived from the amyloid precursor protein (APP) by a gamma secretase-mediated intramembranous cleavage. In addition to amyloid-beta, this cleavage produces a carboxyl-terminal intracellular fragment which has an unknown function. The carboxyl-terminal domain of APP interacts in the cytoplasm with an adapter protein, Fe65. We demonstrate by laser scanning confocal microscopy that a gamma secretase generated APP carboxyl-terminal domain, tagged with green fluorescent protein (GFP), translocates to the nucleus in a manner dependent upon stabilization by the adapter protein Fe65; APP which has been mutated to block interactions with Fe65 cannot be detected in the nucleus. The APP-CT domain continues to interact with Fe65 in the nucleus, as determined by both colocalization and fluorescence resonance energy transfer (FRET). Visualization of the APP-CT-Fe65 complex in the nucleus may serve as a readout for processes that modify gamma secretase release of APP-CT.
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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/APBB1 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/Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Luminescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0022-3042
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
82
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
839-47
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12358789-Active Transport, Cell Nucleus,
pubmed-meshheading:12358789-Amyloid Precursor Protein Secretases,
pubmed-meshheading:12358789-Amyloid beta-Protein Precursor,
pubmed-meshheading:12358789-Aspartic Acid Endopeptidases,
pubmed-meshheading:12358789-Cell Nucleus,
pubmed-meshheading:12358789-Cytoplasm,
pubmed-meshheading:12358789-Endopeptidases,
pubmed-meshheading:12358789-Enzyme Inhibitors,
pubmed-meshheading:12358789-Genes, Reporter,
pubmed-meshheading:12358789-Glioma,
pubmed-meshheading:12358789-Green Fluorescent Proteins,
pubmed-meshheading:12358789-Humans,
pubmed-meshheading:12358789-Luminescent Proteins,
pubmed-meshheading:12358789-Macromolecular Substances,
pubmed-meshheading:12358789-Mutagenesis, Site-Directed,
pubmed-meshheading:12358789-Nerve Tissue Proteins,
pubmed-meshheading:12358789-Nuclear Proteins,
pubmed-meshheading:12358789-Peptide Fragments,
pubmed-meshheading:12358789-Protein Binding,
pubmed-meshheading:12358789-Protein Structure, Tertiary,
pubmed-meshheading:12358789-Recombinant Fusion Proteins,
pubmed-meshheading:12358789-Spectrometry, Fluorescence,
pubmed-meshheading:12358789-Transfection,
pubmed-meshheading:12358789-Tumor Cells, Cultured
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pubmed:year |
2002
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pubmed:articleTitle |
Direct visualization of the gamma secretase-generated carboxyl-terminal domain of the amyloid precursor protein: association with Fe65 and translocation to the nucleus.
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pubmed:affiliation |
Alzheimer Disease Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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