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Article: The relative contribution of CHK1 and CHK2 to Adriamycin-induced checkpoint

TitleThe relative contribution of CHK1 and CHK2 to Adriamycin-induced checkpoint
Authors
Issue Date2005
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yexcr
Citation
Experimental Cell Research, 2005, v. 304 n. 1, p. 1-15 How to Cite?
AbstractTopoisomerase 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. © 2004 Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/88599
ISSN
2015 Impact Factor: 3.378
2015 SCImago Journal Rankings: 1.900
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorHo, CCen_HK
dc.contributor.authorSiu, WYen_HK
dc.contributor.authorChow, JPHen_HK
dc.contributor.authorLau, Aen_HK
dc.contributor.authorArooz, Ten_HK
dc.contributor.authorTong, HYen_HK
dc.contributor.authorNg, IOLen_HK
dc.contributor.authorPoon, RYCen_HK
dc.date.accessioned2010-09-06T09:45:30Z-
dc.date.available2010-09-06T09:45:30Z-
dc.date.issued2005en_HK
dc.identifier.citationExperimental Cell Research, 2005, v. 304 n. 1, p. 1-15en_HK
dc.identifier.issn0014-4827en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88599-
dc.description.abstractTopoisomerase 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. © 2004 Elsevier Inc. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yexcren_HK
dc.relation.ispartofExperimental Cell Researchen_HK
dc.subject.meshBase Sequenceen_HK
dc.subject.meshCell Cycle Proteins - genetics - metabolismen_HK
dc.subject.meshCell Line, Tumoren_HK
dc.subject.meshDNA Damageen_HK
dc.subject.meshDoxorubicin - pharmacologyen_HK
dc.subject.meshGenes, cdcen_HK
dc.subject.meshHeLa Cellsen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMolecular Sequence Dataen_HK
dc.subject.meshNeoplasms - metabolismen_HK
dc.subject.meshProtein Kinases - physiologyen_HK
dc.subject.meshProtein-Serine-Threonine Kinases - physiologyen_HK
dc.subject.meshRNA - metabolismen_HK
dc.titleThe relative contribution of CHK1 and CHK2 to Adriamycin-induced checkpointen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0014-4827&volume=304&issue=1&spage=1&epage=15 &date=2005&atitle=The+relative+contribution+of+CHK1+and+CHK2+to+Adriamycin-induced+checkpointen_HK
dc.identifier.emailNg, IOL:iolng@hkucc.hku.hken_HK
dc.identifier.authorityNg, IOL=rp00335en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.yexcr.2004.10.016en_HK
dc.identifier.pmid15707569-
dc.identifier.scopuseid_2-s2.0-13544251546en_HK
dc.identifier.hkuros105295en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-13544251546&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume304en_HK
dc.identifier.issue1en_HK
dc.identifier.spage1en_HK
dc.identifier.epage15en_HK
dc.identifier.isiWOS:000227127900001-
dc.publisher.placeUnited Statesen_HK

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