Source:http://linkedlifedata.com/resource/pubmed/id/19204928
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
|
| pubmed:dateCreated |
2009-9-1
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| pubmed:abstractText |
Aurora-A, also known as Aik, BTAK, or STK15, is a centrosomal serine/threonine protein kinase, which is proto-oncogenic and is overexpressed in a wide range of human cancers. Besides gene amplification and mRNA overexpression, proteolytic resistance mechanisms are thought to contribute to overexpression of Aurora-A. However, it is not yet clear how overexpressed Aurora-A affects the expression of transformed phenotype. Here, we found that nuclear accumulation of Aurora-A was critical for transformation activity. Cellular protein fractionation experiments and immunoblot analysis demonstrated a predominance of Aurora-A in the nuclear soluble fraction in head and neck cancer cells. Indirect immunofluorescence using confocal laser microscopy confirmed nuclear Aurora-A in head and neck cancer cells, while most oral keratinocytes exhibited only centrosomal localization. The expression of nuclear export signal-fused Aurora-A demonstrated that the oncogenic transformation activity was lost on disruption of the nuclear localization. Thus, the cytoplasmic localization of overexpressed Aurora-A previously demonstrated by immunohistochemical analysis is not likely to correspond to that in intact cancer cells. This study identifies an alternative mode of Aurora-A overexpression in cancer, through nuclear rather than cytoplasmic functions. We suggest that substrates of Aurora-A in the cell nuclear soluble fraction can represent a novel therapeutic target for cancer.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/aurora kinase
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
|
| pubmed:issn |
1098-2744
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
48
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
810-20
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| pubmed:dateRevised |
2011-7-11
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| pubmed:meshHeading |
pubmed-meshheading:19204928-Animals,
pubmed-meshheading:19204928-BALB 3T3 Cells,
pubmed-meshheading:19204928-Cell Line,
pubmed-meshheading:19204928-Cell Line, Tumor,
pubmed-meshheading:19204928-Cell Nucleus,
pubmed-meshheading:19204928-Cell Transformation, Neoplastic,
pubmed-meshheading:19204928-Centrosome,
pubmed-meshheading:19204928-Cytoplasm,
pubmed-meshheading:19204928-Fluorescent Antibody Technique, Indirect,
pubmed-meshheading:19204928-Green Fluorescent Proteins,
pubmed-meshheading:19204928-HeLa Cells,
pubmed-meshheading:19204928-Head and Neck Neoplasms,
pubmed-meshheading:19204928-Humans,
pubmed-meshheading:19204928-Immunoblotting,
pubmed-meshheading:19204928-Immunoprecipitation,
pubmed-meshheading:19204928-Keratinocytes,
pubmed-meshheading:19204928-Mice,
pubmed-meshheading:19204928-Microscopy, Confocal,
pubmed-meshheading:19204928-Polymorphism, Single Nucleotide,
pubmed-meshheading:19204928-Protein-Serine-Threonine Kinases,
pubmed-meshheading:19204928-RNA, Small Interfering,
pubmed-meshheading:19204928-Recombinant Fusion Proteins,
pubmed-meshheading:19204928-Transfection
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| pubmed:year |
2009
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| pubmed:articleTitle |
Oncogenic role of nuclear accumulated Aurora-A.
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| pubmed:affiliation |
Department of Life Sciences, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Hiroshima 727-0023, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|