Linked Life Data

15707569

Source:http://linkedlifedata.com/resource/pubmed/id/15707569

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-2-14
pubmed:abstractText
Topoisomerase II poisons like Adriamycin (ADR, doxorubicin) are clinically important chemotherapeutic agents. Adriamycin-induced DNA damage checkpoint activates ATM and ATR, which could in turn inhibit the cell cycle engine through either CHK1 or CHK2. In this study, we characterized whether CHK1 or CHK2 is required for Adriamycin-induced checkpoint. We found that both CHK1 and CHK2 were phosphorylated after Adriamycin treatment. Several lines of evidence from dominant-negative mutants, short hairpin RNA (shRNA), and knockout cells indicated that CHK1, but not CHK2, is critical for Adriamycin-induced cell cycle arrest. Disruption of CHK1 function bypassed the checkpoint, as manifested by the increase in CDC25A, activation of CDC2, increase in histone H3 phosphorylation, and reduction in cell survival after Adriamycin treatment. In contrast, CHK2 is dispensable for Adriamycin-induced responses. Finally, we found that CHK1 was upregulated in primary hepatocellular carcinoma (HCC), albeit as an inactive form. The presence of a stockpile of dormant CHK1 in cancer cells may have important implications for treatments like topoisomerase II poisons. Collectively, the available data underscore the pivotal role of CHK1 in checkpoint responses to a variety of stresses.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0014-4827
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
304
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1-15
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
The relative contribution of CHK1 and CHK2 to Adriamycin-induced checkpoint.
pubmed:affiliation
Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't