| pubmed-article:10786669 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:10786669 | lifeskim:mentions | umls-concept:C0659150 | lld:lifeskim |
| pubmed-article:10786669 | lifeskim:mentions | umls-concept:C0031727 | lld:lifeskim |
| pubmed-article:10786669 | lifeskim:mentions | umls-concept:C0077681 | lld:lifeskim |
| pubmed-article:10786669 | lifeskim:mentions | umls-concept:C1751194 | lld:lifeskim |
| pubmed-article:10786669 | lifeskim:mentions | umls-concept:C0034541 | lld:lifeskim |
| pubmed-article:10786669 | lifeskim:mentions | umls-concept:C0950721 | lld:lifeskim |
| pubmed-article:10786669 | pubmed:issue | 8 | lld:pubmed |
| pubmed-article:10786669 | pubmed:dateCreated | 2000-5-11 | lld:pubmed |
| pubmed-article:10786669 | pubmed:abstractText | The investigational anticancer agent 7-hydroxystaurosporine (UCN-01) abrogates the G2 checkpoint in tumor cells and sensitizes them to the lethal effects of genotoxic anticancer agents. On the basis of the role of the Cdc25C phosphatase in maintenance of this damage-inducible checkpoint, we hypothesized that UCN-01 inhibits a component of the signal transduction pathway that modulates Cdc25C phosphorylation. Of the three kinases known to phosphorylate Cdc25C on Ser216, both checkpoint kinase 1 (hChk1) and Cdc25C-associated protein kinase 1 (cTAK1) were potently inhibited by UCN-01 with IC50s of 11 and 27 nM, respectively. Treatment of K562 erythroblastoid leukemia cells with similar drug concentrations resulted in decreased levels of Ser216 phosphorylation of Cdc25C and complete disruption of the y-radiation-induced G2 checkpoint. In contrast to hChk1, the hChk2 kinase was 100-fold more resistant to inhibition by UCN-01 (IC50, 1040 nM). These results suggest that disruption of the DNA damage-induced G2 checkpoint by UCN-01 is mediated through the inhibition of the Cdc25C kinases, hChk1 and cTAK1, and that hChk2 activity is not sufficient to enforce the G2 checkpoint in cells treated with a pharmacological inhibitor of hChk1. | lld:pubmed |
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| pubmed-article:10786669 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:10786669 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:10786669 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:10786669 | pubmed:month | Apr | lld:pubmed |
| pubmed-article:10786669 | pubmed:issn | 0008-5472 | lld:pubmed |
| pubmed-article:10786669 | pubmed:author | pubmed-author:AbrahamR TRT | lld:pubmed |
| pubmed-article:10786669 | pubmed:author | pubmed-author:KarnitzL MLM | lld:pubmed |
| pubmed-article:10786669 | pubmed:author | pubmed-author:SarkariaJ NJN | lld:pubmed |
| pubmed-article:10786669 | pubmed:author | pubmed-author:BusbyE CEC | lld:pubmed |
| pubmed-article:10786669 | pubmed:author | pubmed-author:LeistritzD... | lld:pubmed |
| pubmed-article:10786669 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:10786669 | pubmed:day | 15 | lld:pubmed |
| pubmed-article:10786669 | pubmed:volume | 60 | lld:pubmed |
| pubmed-article:10786669 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:10786669 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:10786669 | pubmed:pagination | 2108-12 | lld:pubmed |
| pubmed-article:10786669 | pubmed:dateRevised | 2011-11-2 | lld:pubmed |
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| pubmed-article:10786669 | pubmed:year | 2000 | lld:pubmed |
| pubmed-article:10786669 | pubmed:articleTitle | The radiosensitizing agent 7-hydroxystaurosporine (UCN-01) inhibits the DNA damage checkpoint kinase hChk1. | lld:pubmed |
| pubmed-article:10786669 | pubmed:affiliation | Division of Oncology Research, Mayo Clinic, Rochester, Minnesota 55905, USA. | lld:pubmed |
| pubmed-article:10786669 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:10786669 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| pubmed-article:10786669 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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