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Inhibitors of histone deacetylases induce tumor-selective cytotoxicity through modulating Aurora-A kinase
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Park, Jung-Hyun | - |
dc.contributor.author | Jong, Hyun-Soon | - |
dc.contributor.author | Kim, Sang Gyun | - |
dc.contributor.author | Jung, Yeonjoo | - |
dc.contributor.author | Lee, Keun-Wook | - |
dc.contributor.author | Lee, Ju-Hee | - |
dc.contributor.author | Kim, Dae-Kee | - |
dc.contributor.author | Bang, Yung-Jue | - |
dc.contributor.author | Kim, Tae-You | - |
dc.date.accessioned | 2010-03-31T04:46:27Z | - |
dc.date.available | 2010-03-31T04:46:27Z | - |
dc.date.created | 2020-12-21 | - |
dc.date.issued | 2008-01 | - |
dc.identifier.citation | Journal of Molecular Medicine, Vol.86 No.1, pp.117-128 | - |
dc.identifier.issn | 0946-2716 | - |
dc.identifier.other | 119472 | - |
dc.identifier.uri | https://hdl.handle.net/10371/62183 | - |
dc.description.abstract | The molecular basis of the antitumor selectivity of histone deacetylase inhibitors (HDIs) remains unclear. Centrosomal Aurora-A kinase regulates chromosomal segregation during mitosis. The overexpression or amplification of Aurora-A leads to genetic instability, and its inhibition has shown significant antitumor effects. In this paper, we report that structurally related hydroxamate LAQ824 and SK-7068 induce tumor-selective mitotic defects by depleting Aurora-A. We found that HDI-treated cancer cells, unlike nontransformed cells, exhibit defective mitotic spindles. After HDI, Aurora-A was selectively downregulated in cancer cells, whereas Aurora-B remained unchanged in both cancer and nontransformed cells. LAQ824 or SK-7068 treatment inhibited histone deacetylase (HDAC) 6 present in Aurora-A/heat shock protein (Hsp) 90 complex. Inhibition of HDAC6 acetylated Hsp90 and resulted in dissociation of acetylated Hsp90 from Aurora-A. As a result, Hsp70 binding to Aurora-A was enhanced in cancer cells, leading to proteasomal degradation of Aurora-A. Overall, these provide a novel molecular basis of tumor selectivity of HDI. LAQ824 and SK-7068 might be more effective HDIs in cancer cells with Aurora-A overexpression. | - |
dc.language | 영어 | - |
dc.language.iso | en | en |
dc.publisher | Springer Verlag | - |
dc.title | Inhibitors of histone deacetylases induce tumor-selective cytotoxicity through modulating Aurora-A kinase | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 방영주 | - |
dc.identifier.doi | 10.1007/s00109-007-0260-8 | - |
dc.citation.journaltitle | Journal of Molecular Medicine | - |
dc.identifier.wosid | 000252279400012 | - |
dc.identifier.scopusid | 2-s2.0-38149093282 | - |
dc.citation.endpage | 128 | - |
dc.citation.number | 1 | - |
dc.citation.startpage | 117 | - |
dc.citation.volume | 86 | - |
dc.identifier.sci | 000252279400012 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Bang, Yung-Jue | - |
dc.contributor.affiliatedAuthor | Kim, Tae-You | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | ACUTE MYELOID-LEUKEMIA | - |
dc.subject.keywordPlus | CANCER CELLS | - |
dc.subject.keywordPlus | IN-VIVO | - |
dc.subject.keywordPlus | HETEROCHROMATIN | - |
dc.subject.keywordPlus | TRICHOSTATIN | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordPlus | ACETYLATION | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | PATHWAY | - |
dc.subject.keywordAuthor | histone deacetylase inhibitor | - |
dc.subject.keywordAuthor | Aurora-A | - |
dc.subject.keywordAuthor | LAQ824 | - |
dc.subject.keywordAuthor | SK-7068 | - |
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