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dc.contributor.author임형신-
dc.date.accessioned2019-04-16T02:08:55Z-
dc.date.available2019-04-16T02:08:55Z-
dc.date.issued2015-12-
dc.identifier.citationJOURNAL OF CELLULAR PHYSIOLOGY, v. 230, No. 12, Page. 3057-3067en_US
dc.identifier.issn0021-9541-
dc.identifier.issn1097-4652-
dc.identifier.urihttp://onlinelibrary.wiley.com/doi/10.1002/jcp.25042/full-
dc.identifier.urihttps://repository.hanyang.ac.kr/handle/20.500.11754/102044-
dc.description.abstractThe expression of polo-like kinase 1 (Plk1) correlates with malignancy and is thus recognized as a target for cancer therapy. In addition to the development of ATP-competitive Plk1 inhibitors, the polo-box domain (PBD), a unique functional domain of PLKs, is being targeted to develop Plk1-specific inhibitors. However, the action mechanisms of these two classes of Plk1 inhibitors have not been thoroughly evaluated. Here, we evaluate the differences in cellular effects of ATP-binding domain inhibitors (BI 2536, GSK 461364) and PBD inhibitors (poloxin, thymoquinone) to determine their mechanisms of Plk1 inhibition. Our data show that BI 2536 and GSK461364 increased the population of cells in the G2/M phase compared with controls, while treatment with poloxin and thymoquinone increased cell population in the S phase as well as in G2/M, in a p53-independent manner. The population of cells staining positively for p-Histone H3 and MPM2, mitotic index, was increased by treatment with BI 2536 or GSK461364, but not by treatment with poloxin or thymoquinone. Furthermore, treatment with BI 2536 or GSK461364 resulted in activation of the BubR1 spindle checkpoint kinase, suggesting that treatment with ATP-binding domain inhibitors induces metaphase arrest. However, the administration of poloxin and thymoquinone resulted in an increase in p21(WAF1) and S arrest, indicating that PBD inhibitors also affected interphase before mitotic entry. Taken together, these data suggest that the PDB of Plk1 plays a role in S phase progression through interaction with other proteins, while its ATP-binding domain is important for regulating mitotic progression mediated by its catalytic activity involving consumption of ATP. (C) 2015 Wiley Periodicals, Inc.en_US
dc.description.sponsorshipContract grant sponsor: National Research Foundation of Korea (NRF) (Ministry of Science, ICT and Future Planning); Contract grant number: NRF-2012R1A1A1011382 NRF-2014R1A2A1A11049701.en_US
dc.language.isoen_USen_US
dc.publisherWILEY-BLACKWELLen_US
dc.subjectDNA-DAMAGE CHECKPOINTen_US
dc.subjectCANCER-CELLSen_US
dc.subjectCYCLE ARRESTen_US
dc.subjectKINASE 1en_US
dc.subjectTHYMOQUINONEen_US
dc.subjectPOLO-LIKE-KINASE-1en_US
dc.subjectDEPLETIONen_US
dc.subjectPROGRESSIONen_US
dc.subjectREGULATORen_US
dc.subjectDISCOVERYen_US
dc.titleDifferential Cellular Effects of Plk1 Inhibitors Targeting the ATP-binding Domain or Polo-box Domainen_US
dc.typeArticleen_US
dc.relation.no12-
dc.relation.volume230-
dc.identifier.doi10.1002/jcp.25042-
dc.relation.page3057-3067-
dc.relation.journalJOURNAL OF CELLULAR PHYSIOLOGY-
dc.contributor.googleauthorShin, Sol-Bi-
dc.contributor.googleauthorWoo, Sang-Uk-
dc.contributor.googleauthorYim, Hyungshin-
dc.relation.code2015000519-
dc.sector.campusE-
dc.sector.daehakCOLLEGE OF PHARMACY[E]-
dc.sector.departmentDEPARTMENT OF PHARMACY-
dc.identifier.pidhsyim-
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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