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Functional p53 in cells contributes to the anticancer effect of the cyclin-dependent kinase inhibitor roscovitine
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SYSNO ASEP 0335831 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Functional p53 in cells contributes to the anticancer effect of the cyclin-dependent kinase inhibitor roscovitine Title Funkční p53 v buňkách přispívá k protinádorovému účinku roskovitinu Author(s) Paprskářová, Martina (UEB-Q)
Kryštof, Vladimír (UEB-Q) RID, ORCID
Jorda, Radek (UEB-Q) ORCID, RID
Džubák, P. (CZ)
Hajdúch, M. (CZ)
Wesierska-Gadek, J. (AT)
Strnad, Miroslav (UEB-Q) RID, ORCIDSource Title Journal of Cellular Biochemistry. - : Wiley - ISSN 0730-2312
Roč. 107, č. 3 (2009), s. 428-437Number of pages 10 s. Language eng - English Country US - United States Keywords APOPTOSIS ; CYCLIN-DEPENDENT KINASE ; OLOMOUCINE II ; p53 Subject RIV EB - Genetics ; Molecular Biology R&D Projects GA204/08/0511 GA ČR - Czech Science Foundation (CSF) CEZ AV0Z50380511 - UEB-Q (2005-2011) UT WOS 000266872300007 DOI 10.1002/jcb.22139 Annotation To define the role of p53 in the anticancer effect of selective CDK inhibitors, two related compounds roscovitine and olomoucine II were studied. Roscovitine differs functionally from its congener olomoucine II only in the selectivity towards transcriptional CDK9. Action of both compounds on proliferation, cell cycle progression and apoptosis was examined in RPMI-8226 cells expressing the temperature-sensitive mutant of p53 and in MCF-7 cells with wild-type p53. Both compounds blocked proliferation, decreased phosphorylation of RNA polymerase II, downregulated anti-apoptotic protein Mcl-1 in both cell lines in a dose-dependent manner, and also activated p53 in MCF-7 cells. Moreover, we showed that the anticancer efficiency of CDK inhibitors was enhanced by active p53 in RPMI-8226 cells kept at permissive temperature, where downregulation of Mcl-1, fragmentation of PARP-1 and increased caspase-3 activity was detected with lower doses of the compounds. Workplace Institute of Experimental Botany Contact David Klier, knihovna@ueb.cas.cz, Tel.: 220 390 469 Year of Publishing 2010
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