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rdf:type |
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lifeskim:mentions |
umls-concept:C0033268,
umls-concept:C0033684,
umls-concept:C0085862,
umls-concept:C0086597,
umls-concept:C0441712,
umls-concept:C0597298,
umls-concept:C0851827,
umls-concept:C1299583,
umls-concept:C1412457,
umls-concept:C1423773,
umls-concept:C1549571,
umls-concept:C1608386,
umls-concept:C1701901,
umls-concept:C1743100
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pubmed:issue |
Pt 1
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pubmed:dateCreated |
2003-8-7
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pubmed:abstractText |
XB51 (derived from X11-like binding protein of clone number 51) was isolated by yeast two-hybrid cDNA screening using the N-terminal domain of X11L (X11-like protein) as a bait. X11L is a neuron-specific adaptor protein that is known to down-regulate APP (beta-amyloid precursor protein) metabolism by associating with the cytoplasmic domain of APP, but the detailed mechanisms are still unknown. Thus the X11L-associated protein XB51 is believed to regulate APP metabolism by modifying X11L function through its interaction with X11L. Here we report that the hXB51 (human XB51 ) gene can yield two transcripts, one with exon 9 spliced out (resulting in the hXB51beta isoform) and the other containing exon 9 (yielding the hXB51alpha isoform). hXB51alpha binds to X11L to form a tripartite complex composed of hXB51alpha, X11L and APP. Complex-formation results in blocking X11L's suppression of Abeta (beta-amyloid) generation from APP. hXB51beta associates with X11L and inhibits its interaction with APP. However, hXB51beta suppresses Abeta generation and secretion in an X11L-independent manner. Thus the hXB51 isoforms regulate Abeta generation differently, either enhancing it by modifying the association of X11L with APP or suppressing it in an X11L-independent manner. These observations advance our understanding of the molecular mechanisms regulating intracellular Abeta production and the pathogenesis of Alzheimer's disease.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-10049767,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-10336668,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-10777610,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-10833507,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-10846156,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-10846187,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-11036064,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-11273707,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-11274343,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-11517218,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-11517249,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-11572975,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-11823626,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-11912189,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-12016213,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-12023290,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-12044471,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-7678331,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-8021238,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-8537337,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-9085254,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-9446595,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-9497354,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-9614075,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-9804539,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-9843960,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12780348-9890987
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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/APBA1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/NECAB3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0264-6021
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
374
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
261-8
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:12780348-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:12780348-Amyloid beta-Peptides,
pubmed-meshheading:12780348-Base Sequence,
pubmed-meshheading:12780348-Binding Sites,
pubmed-meshheading:12780348-Carrier Proteins,
pubmed-meshheading:12780348-Cloning, Molecular,
pubmed-meshheading:12780348-DNA, Complementary,
pubmed-meshheading:12780348-DNA Primers,
pubmed-meshheading:12780348-Gene Expression Regulation,
pubmed-meshheading:12780348-Humans,
pubmed-meshheading:12780348-Nerve Tissue Proteins,
pubmed-meshheading:12780348-Plasmids,
pubmed-meshheading:12780348-Protein Binding,
pubmed-meshheading:12780348-Protein Isoforms,
pubmed-meshheading:12780348-Recombinant Proteins
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pubmed:year |
2003
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pubmed:articleTitle |
XB51 isoforms mediate Alzheimer's beta-amyloid peptide production by X11L (X11-like protein)-dependent and -independent mechanisms.
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pubmed:affiliation |
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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