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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F05%3A00002165" target="_blank" >RIV/61989592:15310/05:00002165 - isvavai.cz</a>

Alternative codes found

RIV/00209805:_____/05:#0000023 RIV/61389030:_____/05:00343928

Result on the web

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DOI - Digital Object Identifier

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Result language

angličtina

Original language name

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

Original language description

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 cocrystal 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-typep53 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 cyclindependent kinase inhibitors.

Czech name

aktivita olomoucinu, nového inhibitoru cyklin-dependentních kinas

Czech description

Práce popisuje inhibiční profil olomoucinu II a na základě rentgenostrukturní analýzy také orientaci molekuly v aktivním místě CDK2. Olomoucin II vykazuje výraznou selektivitu k CDK7 a CDK9, které mají důležité funkce při regulaci transkripce RNA. Buněčné působení inhibitoru je provázeno aktivací nádorového supresoru p53 a jím řízeného genu p21WAF1. Navíc dochází v buňkách k destrukci jadérek, provázených uvolněním proteinu L11 a jeho vazbu na Hdm2, což může přispívat ke stabilizaci p53.

Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EF - Botany

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

Z - Vyzkumny zamer (s odkazem do CEZ)

Publication year

2005

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cellular and Molecular Life Sciences

ISSN

1420-682X

e-ISSN

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Volume of the periodical

62

Issue of the periodical within the volume

15

Country of publishing house

CH - SWITZERLAND

Number of pages

31

Pages from-to

1763-71

UT code for WoS article

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EID of the result in the Scopus database

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