Počet záznamů: 1  

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

  1. 1. 0343928 - UEB-Q 2011 RIV CH eng J - Článek v odborném periodiku
    Kryštof, Vladimír - McNae, I. W. - Walkinshaw, M. D. - Fischer, P.M. - Müller, P. - Vojtešek, B. - Orság, Martin - Havlíček, Libor - Strnad, Miroslav
    Antiproliferative activity of olomoucine II, a novel 2,6,9-trisubstituted purine cyclin-dependent kinase inhibitor.
    Cellular and Molecular Life Sciences. Roč. 62, č. 15 (2005), s. 1763-1771. ISSN 1420-682X
    Grant CEP: GA ČR GP204/03/D231
    Výzkumný záměr: CEZ:AV0Z50380511
    Klíčová slova: olomoucine II * roscovitine * cyclin-dependent kinase inhibitor
    Kód oboru RIV: CE - Biochemie
    Impakt faktor: 4.582, rok: 2005

    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.
    Trvalý link: http://hdl.handle.net/11104/0186288