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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
17
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pubmed:dateCreated |
2000-6-2
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pubmed:abstractText |
It is widely believed that one of the causes of Alzheimer's disease (AD) is the generation and secretion of beta-amyloid (Abeta) from amyloid precursor protein in the brain. Here we report that a transcription factor, NF-kappaB/p65, induces increased secretion of amyloidogenic Abeta42 but not Abeta40. The kappaB motif-dependent production of Abeta42 was suppressed by binding of NF-kappaB/p65 to the PDZ domain of the X11-like protein (X11L), which a human homologue protein of LIN-10. The results suggest that the PDZ domain of X11L can control the ability of NF-kappaB/p65 to induce expression of protein(s) involved in Abeta42 production. The amino acids 161-163 in Rel homology domain (RHD) of NF-kappaB/p65 is important in interaction of NF-kappaB/p65 with X11L. Another subunit NF-kappaB/p50 and heterodimers of p65 and p50 do not bind to X11L. Our finding indicates NF-kappaB and X11L may, in novel way, regulate Abeta production in neuronal cells. Targeting X11L by specific therapy may provide the possibility to control the progression of AD.
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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/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B p50 Subunit,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor RelA,
http://linkedlifedata.com/resource/pubmed/chemical/amyloid beta-protein (1-40),
http://linkedlifedata.com/resource/pubmed/chemical/amyloid beta-protein (1-42)
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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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 |
28
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pubmed:volume |
275
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
13056-60
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:10777610-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:10777610-Alzheimer Disease,
pubmed-meshheading:10777610-Amyloid beta-Peptides,
pubmed-meshheading:10777610-Animals,
pubmed-meshheading:10777610-Brain,
pubmed-meshheading:10777610-COS Cells,
pubmed-meshheading:10777610-Cell Line,
pubmed-meshheading:10777610-DNA, Complementary,
pubmed-meshheading:10777610-Gene Expression Regulation,
pubmed-meshheading:10777610-Gene Library,
pubmed-meshheading:10777610-Humans,
pubmed-meshheading:10777610-Luciferases,
pubmed-meshheading:10777610-NF-kappa B,
pubmed-meshheading:10777610-NF-kappa B p50 Subunit,
pubmed-meshheading:10777610-Nerve Tissue Proteins,
pubmed-meshheading:10777610-Neurons,
pubmed-meshheading:10777610-Peptide Fragments,
pubmed-meshheading:10777610-Precipitin Tests,
pubmed-meshheading:10777610-Protein Binding,
pubmed-meshheading:10777610-Protein Isoforms,
pubmed-meshheading:10777610-Protein Structure, Tertiary,
pubmed-meshheading:10777610-Transcription, Genetic,
pubmed-meshheading:10777610-Transcription Factor RelA,
pubmed-meshheading:10777610-Transfection,
pubmed-meshheading:10777610-Two-Hybrid System Techniques
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pubmed:year |
2000
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pubmed:articleTitle |
PDZ domain-dependent suppression of NF-kappaB/p65-induced Abeta42 production by a neuron-specific X11-like protein.
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pubmed:affiliation |
Laboratory of Neurobiophysics, 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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