rdf:type |
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lifeskim:mentions |
umls-concept:C0007102,
umls-concept:C0026237,
umls-concept:C0033414,
umls-concept:C0079419,
umls-concept:C0162638,
umls-concept:C0334227,
umls-concept:C0441472,
umls-concept:C0700114,
umls-concept:C1070653,
umls-concept:C1425143,
umls-concept:C1879547
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pubmed:issue |
3
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pubmed:dateCreated |
2007-3-16
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pubmed:abstractText |
Targeting the ubiquitin-proteasome degradation pathway has become a promising approach for cancer therapy. Previous studies have shown that proteasome inhibition leads to apoptosis in various cancer cells. The mechanism by which apoptosis occurs are not fully understood and can be cell type and/or inhibitor specific. In this study, we investigated the mechanism of mitochondrial activation by proteasome inhibitors in colon cancer cells. We found that Bax activation and mitochondria translocation were required for apoptosis induced by multiple proteasome inhibitors. In contrast, reactive oxygen species did not seem to be induced by MG132 or bortezomib and antioxidants had no effects on MG132-induced apoptosis. In contrast, treatment with MG132 or bortezomib induced a significant accumulation of p53 and PUMA. Genetic deletion of either p53 or PUMA led to a marked suppression of apoptosis induced by these inhibitors, accompanied with reduced Bax activation and cytochrome c release. Consistently, inhibition of translation by cycloheximide could also effectively abolish the accumulation of p53 and PUMA and suppress MG132-induced Bax activation and apoptosis. These findings thus strongly indicate the critical involvement of p53-, PUMA-, and Bax-mediated mitochondrial activation in proteasome inhibitor-induced apoptosis in colon cancer cells.
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pubmed:grant |
|
pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/BAX protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/BBC3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Boronic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochromes c,
http://linkedlifedata.com/resource/pubmed/chemical/Leupeptins,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrazines,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-2-Associated X Protein,
http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonylleucyl-leucyl-leuci...,
http://linkedlifedata.com/resource/pubmed/chemical/bortezomib
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
|
pubmed:issn |
1535-7163
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:volume |
6
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1062-9
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pubmed:dateRevised |
2007-12-3
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pubmed:meshHeading |
pubmed-meshheading:17363499-Animals,
pubmed-meshheading:17363499-Apoptosis,
pubmed-meshheading:17363499-Apoptosis Regulatory Proteins,
pubmed-meshheading:17363499-Boronic Acids,
pubmed-meshheading:17363499-Caspases,
pubmed-meshheading:17363499-Cell Nucleus,
pubmed-meshheading:17363499-Colonic Neoplasms,
pubmed-meshheading:17363499-Cysteine Proteinase Inhibitors,
pubmed-meshheading:17363499-Cytochromes c,
pubmed-meshheading:17363499-Humans,
pubmed-meshheading:17363499-Leupeptins,
pubmed-meshheading:17363499-Mice,
pubmed-meshheading:17363499-Mitochondria,
pubmed-meshheading:17363499-Proteasome Endopeptidase Complex,
pubmed-meshheading:17363499-Protein Transport,
pubmed-meshheading:17363499-Proto-Oncogene Proteins,
pubmed-meshheading:17363499-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:17363499-Pyrazines,
pubmed-meshheading:17363499-Reactive Oxygen Species,
pubmed-meshheading:17363499-Tumor Cells, Cultured,
pubmed-meshheading:17363499-Tumor Suppressor Protein p53,
pubmed-meshheading:17363499-bcl-2-Associated X Protein
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pubmed:year |
2007
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pubmed:articleTitle |
A coordinated action of Bax, PUMA, and p53 promotes MG132-induced mitochondria activation and apoptosis in colon cancer cells.
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pubmed:affiliation |
Department of Pathology, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA 15231, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|