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rdf:type |
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lifeskim:mentions |
umls-concept:C0015576,
umls-concept:C0033684,
umls-concept:C0162589,
umls-concept:C0178719,
umls-concept:C0379528,
umls-concept:C0596311,
umls-concept:C0851285,
umls-concept:C0870733,
umls-concept:C1167622,
umls-concept:C1330957,
umls-concept:C1364818,
umls-concept:C1412459,
umls-concept:C1514562,
umls-concept:C1518440,
umls-concept:C1533134,
umls-concept:C1707271,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221
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pubmed:issue |
22
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pubmed:dateCreated |
2003-6-3
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pubmed:abstractText |
Regulated intramembrane proteolysis (RIP) of the amyloid precursor protein (APP) produces amyloid beta-protein (Abeta), the probable causative agent of Alzheimer's disease (AD), and is therefore an important target for therapeutic intervention. However, there is a burgeoning consensus that gamma-secretase, one of the proteases that generates Abeta, is also critical for the signal transduction of APP and a growing list of other receptors. APP is a member of a gene family that includes two amyloid precursor-like proteins, APLP1 and APLP2. Although APP and the APLPs undergo similar proteolytic processing, there is little information about the role of their gamma-secretase-generated intracellular domains (ICDs). Here, we show that APLP1 and 2 undergo presenilin-dependent RIP similar to APP, resulting in the release of a approximately 6 kDa ICD for each protein. Each of the ICDs are degraded by an insulin degrading enzyme-like activity, but they can be stabilized by members of the FE65 family and translocate to the nucleus. Given that modulation of APP processing is a therapeutic target and that the APLPs are processed in a manner similar to APP, any strategy aimed at altering APP proteolysis will have to take into account possible effects on signaling by APLP 1 and 2.
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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/APLP1 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/Apbb1 protein, mouse,
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/Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0006-2960
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
42
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6664-73
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12779321-Amino Acid Sequence,
pubmed-meshheading:12779321-Amyloid Precursor Protein Secretases,
pubmed-meshheading:12779321-Amyloid beta-Protein Precursor,
pubmed-meshheading:12779321-Animals,
pubmed-meshheading:12779321-Aspartic Acid Endopeptidases,
pubmed-meshheading:12779321-CHO Cells,
pubmed-meshheading:12779321-COS Cells,
pubmed-meshheading:12779321-Cell Membrane,
pubmed-meshheading:12779321-Cell Nucleus,
pubmed-meshheading:12779321-Cloning, Molecular,
pubmed-meshheading:12779321-Cricetinae,
pubmed-meshheading:12779321-Endopeptidases,
pubmed-meshheading:12779321-Fluorescent Antibody Technique, Direct,
pubmed-meshheading:12779321-Humans,
pubmed-meshheading:12779321-Molecular Sequence Data,
pubmed-meshheading:12779321-Nerve Tissue Proteins,
pubmed-meshheading:12779321-Nuclear Proteins,
pubmed-meshheading:12779321-Protein Binding,
pubmed-meshheading:12779321-Protein Processing, Post-Translational,
pubmed-meshheading:12779321-Protein Structure, Tertiary,
pubmed-meshheading:12779321-Recombinant Proteins,
pubmed-meshheading:12779321-Signal Transduction
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pubmed:year |
2003
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pubmed:articleTitle |
gamma-Secretase cleavage and binding to FE65 regulate the nuclear translocation of the intracellular C-terminal domain (ICD) of the APP family of proteins.
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pubmed:affiliation |
Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
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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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