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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2003-4-15
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pubmed:abstractText |
APP-BP1, first identified as a protein that interacts with the carboxyl (C) terminus of the amyloid precursor protein (APP), is one-half of the bipartite activating enzyme for the ubiquitin-like protein NEDD8. We report here that APP-BP1 also specifically interacts with apoptosis stimulating protein of p53 ASPP2 in non-transfected cells through the functional predominant N-terminal domain ASPP2(332-483). ASPP2 inhibits the ability of APP-BP1 to rescue the ts41 cell cycle mutation and inhibits APP-BP1 induced apoptosis in primary neurons. ASPP2 reduces the ability of NEDD8 to conjugate to Cullin-1, inhibits APP-BP1-dependent ts41 cell proliferation, and blocks the ability of APP-BP1 to cause apoptosis and to cause DNA synthesis in neurons. We also show that ASPP2 activates nuclear factor-kappaB (NF-kappaB) transcriptional activity, which seems to be inhibited by the neddylation pathway since the dominant negative NEDD8 activating enzyme causes enhanced NF-kappaB activity. Our data provide the first in vivo evidence that ASPP2 is a negative regulator of the neddylation pathway through specific interaction with APP-BP1 and suggest that dysfunction of the APP-BP1 interaction with APP may be one cause of Alzheimer's disease.
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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/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cullin 1,
http://linkedlifedata.com/resource/pubmed/chemical/Cullin Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/NEDD8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Subunits,
http://linkedlifedata.com/resource/pubmed/chemical/TP53BP2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitins,
http://linkedlifedata.com/resource/pubmed/chemical/amyloid protein precursor-binding...
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pubmed:status |
MEDLINE
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pubmed:month |
May
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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 |
85
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
801-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12694406-Animals,
pubmed-meshheading:12694406-Apoptosis,
pubmed-meshheading:12694406-Apoptosis Regulatory Proteins,
pubmed-meshheading:12694406-Carrier Proteins,
pubmed-meshheading:12694406-Cell Cycle Proteins,
pubmed-meshheading:12694406-Cell Division,
pubmed-meshheading:12694406-Cells, Cultured,
pubmed-meshheading:12694406-Cricetinae,
pubmed-meshheading:12694406-Cullin Proteins,
pubmed-meshheading:12694406-DNA,
pubmed-meshheading:12694406-DNA-Binding Proteins,
pubmed-meshheading:12694406-Humans,
pubmed-meshheading:12694406-Macromolecular Substances,
pubmed-meshheading:12694406-NF-kappa B,
pubmed-meshheading:12694406-Neurons,
pubmed-meshheading:12694406-Protein Binding,
pubmed-meshheading:12694406-Protein Subunits,
pubmed-meshheading:12694406-Rats,
pubmed-meshheading:12694406-Rats, Sprague-Dawley,
pubmed-meshheading:12694406-Signal Transduction,
pubmed-meshheading:12694406-Ubiquitins
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pubmed:year |
2003
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pubmed:articleTitle |
ASPP2 inhibits APP-BP1-mediated NEDD8 conjugation to cullin-1 and decreases APP-BP1-induced cell proliferation and neuronal apoptosis.
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pubmed:affiliation |
Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts, USA. ychen@helix.mgh.harvard.edu
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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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