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rdf:type |
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lifeskim:mentions |
umls-concept:C0007610,
umls-concept:C0033684,
umls-concept:C0178719,
umls-concept:C0184512,
umls-concept:C1412459,
umls-concept:C1514562,
umls-concept:C1709634,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221,
umls-concept:C2353566
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pubmed:issue |
43
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pubmed:dateCreated |
2001-10-22
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pubmed:abstractText |
The beta-amyloid precursor protein (APP) is a ubiquitous receptor-like molecule without a known function. However, the recent recognition that APP and Notch undergo highly similar proteolytic processing has suggested a potential signaling function for APP. After ligand binding, Notch is cleaved by the ADAM-17 metalloprotease followed by an intramembrane cleavage mediated by gamma-secretase. The gamma-secretase cut releases the Notch intracellular domain (NICD), which enters the nucleus and modulates transcription. Because APP is processed similarly by ADAM-17 and gamma-secretase, we reasoned that the APP intracellular domain (AICD) has a role analogous to the NICD. We therefore generated a plasmid encoding the AICD sequence and studied the subcellular localization of the expressed protein (C60). Our results demonstrate that the cytoplasmic domain of APP is a highly labile fragment that is stabilized by forming complexes with Fe65 and can then enter the nucleus in neurons and non-neural cells. These findings strongly support the hypothesis that APP signals in the nucleus in a manner analogous to the function of Notch.
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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/ADAM Proteins,
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/CREB-Binding Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Drosophila Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases,
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/Receptors, Notch,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/suppressor of Hairless protein...,
http://linkedlifedata.com/resource/pubmed/chemical/tumor necrosis factor-alpha...
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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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 |
26
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
40288-92
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11544248-ADAM Proteins,
pubmed-meshheading:11544248-Active Transport, Cell Nucleus,
pubmed-meshheading:11544248-Amyloid Precursor Protein Secretases,
pubmed-meshheading:11544248-Amyloid beta-Protein Precursor,
pubmed-meshheading:11544248-Aspartic Acid Endopeptidases,
pubmed-meshheading:11544248-CREB-Binding Protein,
pubmed-meshheading:11544248-Drosophila Proteins,
pubmed-meshheading:11544248-Endopeptidases,
pubmed-meshheading:11544248-Half-Life,
pubmed-meshheading:11544248-Membrane Proteins,
pubmed-meshheading:11544248-Metalloendopeptidases,
pubmed-meshheading:11544248-Nerve Tissue Proteins,
pubmed-meshheading:11544248-Nuclear Proteins,
pubmed-meshheading:11544248-Peptide Fragments,
pubmed-meshheading:11544248-Protein Binding,
pubmed-meshheading:11544248-Protein Processing, Post-Translational,
pubmed-meshheading:11544248-Receptors, Notch,
pubmed-meshheading:11544248-Repressor Proteins,
pubmed-meshheading:11544248-Signal Transduction,
pubmed-meshheading:11544248-Trans-Activators
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pubmed:year |
2001
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pubmed:articleTitle |
The intracellular domain of the beta-amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a notch-like manner.
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pubmed:affiliation |
Department of Neurology, Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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