Počet záznamů: 1

Antiproliferative activity of olomoucine II, a novel 2,6,9-trisubstituted purine cyclin-dependent kinase inhibitor

SYSNO ASEP	0343928
Druh ASEP	J - Článek v odborném periodiku
Zařazení RIV	J - Článek v odborném periodiku
Poddruh J	Článek ve WOS
Název	Antiproliferative activity of olomoucine II, a novel 2,6,9-trisubstituted purine cyclin-dependent kinase inhibitor
Tvůrce(i)	Kryštof, Vladimír (UEB-Q)_{RID, ORCID} McNae, I. W. (GB) Walkinshaw, M. D. (GB) Fischer, P.M. (GB) Müller, P. (CZ) Vojtešek, B. (CZ) Orság, Martin (UEB-Q) Havlíček, Libor (UEB-Q)_{RID, ORCID} Strnad, Miroslav (UEB-Q)_{RID, ORCID}
Zdroj.dok.	Cellular and Molecular Life Sciences - ISSN 1420-682X Roč. 62, č. 15 (2005), s. 1763-1771
Poč.str.	9 s.
Jazyk dok.	eng - angličtina
Země vyd.	CH - Švýcarsko
Klíč. slova	olomoucine II ; roscovitine ; cyclin-dependent kinase inhibitor
Vědní obor RIV	CE - Biochemie
CEP	GP204/03/D231 GA ČR - Grantová agentura ČR
CEZ	AV0Z50380511 - UEB-Q (2005-2011)
UT WOS	000232497200011
DOI	10.1007/s00018-005-5185-1
Anotace	The study describes the protein kinase selectivity profile, as well as the binding mode of olomoucine II in the catalytic cleft of CDK2, as determined from co-crystal analysis. Apart from the main cell cycle-regulating kinase CDK2, olomoucine II exerts specificity for CDK7 and CDK9, with important functions in the regulation of RNA transcription. In vitro anticancer activity of the inhibitor in a panel of tumor cell lines shows a wide potency range with a slight preference for cells harboring a wild-type p53 gene. Cell-based assays confirmed activation of p53 protein levels and events leading to accumulation of p21(WAF1). Additionally, in olomoucine II-treated cells, Mdm2 was found to form a complex with the ribosomal protein L11, which inhibits Mdm2 ubiquitin ligase function. We conclude that perturbations in RNA synthesis may lead to activation of p53 and that this contributes to the antiproliferative potency of cyclin-dependent kinase inhibitors.
Pracoviště	Ústav experimentální botaniky
Kontakt	David Klier, knihovna@ueb.cas.cz, Tel.: 220 390 469
Rok sběru	2011

Počet záznamů: 1