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rdf:type |
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lifeskim:mentions |
umls-concept:C0002716,
umls-concept:C0007586,
umls-concept:C0007634,
umls-concept:C0013126,
umls-concept:C0015127,
umls-concept:C0027882,
umls-concept:C0033684,
umls-concept:C0162638,
umls-concept:C1314792,
umls-concept:C1622642,
umls-concept:C1709634
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pubmed:issue |
12
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pubmed:dateCreated |
2000-4-27
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pubmed:abstractText |
APP-BP1 binds to the amyloid precursor protein (APP) carboxyl-terminal domain. Recent work suggests that APP-BP1 participates in a novel ubiquitinylation-related pathway involving the ubiquitin-like molecule NEDD8. We show here that, in vivo in mammalian cells, APP-BP1 interacts with hUba3, its presumptive partner in the NEDD8 activation pathway, and that the APP-BP1 binding site for hUba3 is within amino acids 443-479. We also provide evidence that the human APP-BP1 molecule can rescue the ts41 mutation in Chinese hamster cells. This mutation previously has been shown to lead to successive S phases of the cell cycle without intervening G(2), M, and G(1), suggesting that the product of this gene negatively regulates entry into the S phase and positively regulates entry into mitosis. We show that expression of APP-BP1 in ts41 cells drives the cell cycle through the S-M checkpoint and that this function requires both hUba3 and hUbc12. Overexpression of APP-BP1 in primary neurons causes apoptosis via the same pathway. A specific caspase-6 inhibitor blocks this apoptosis. These findings are discussed in the context of abnormalities in the cell cycle that have been observed in 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/CASP6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Casp6 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 6,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NEDD8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Saccharomyces cerevisiae Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/UBA3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/UBC12 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Activating Enzymes,
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 |
Mar
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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 |
24
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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 |
8929-35
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pubmed:dateRevised |
2008-8-21
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pubmed:meshHeading |
pubmed-meshheading:10722740-Alzheimer Disease,
pubmed-meshheading:10722740-Animals,
pubmed-meshheading:10722740-Apoptosis,
pubmed-meshheading:10722740-Caspase 6,
pubmed-meshheading:10722740-Caspases,
pubmed-meshheading:10722740-Cerebral Cortex,
pubmed-meshheading:10722740-Cricetinae,
pubmed-meshheading:10722740-DNA-Binding Proteins,
pubmed-meshheading:10722740-Genetic Complementation Test,
pubmed-meshheading:10722740-Humans,
pubmed-meshheading:10722740-Mitosis,
pubmed-meshheading:10722740-Neurons,
pubmed-meshheading:10722740-Precipitin Tests,
pubmed-meshheading:10722740-Protein Binding,
pubmed-meshheading:10722740-Rats,
pubmed-meshheading:10722740-S Phase,
pubmed-meshheading:10722740-Saccharomyces cerevisiae Proteins,
pubmed-meshheading:10722740-Two-Hybrid System Techniques,
pubmed-meshheading:10722740-Ubiquitin-Activating Enzymes,
pubmed-meshheading:10722740-Ubiquitins
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pubmed:year |
2000
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pubmed:articleTitle |
The amyloid precursor protein-binding protein APP-BP1 drives the cell cycle through the S-M checkpoint and causes apoptosis in neurons.
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pubmed:affiliation |
Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts 02478, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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