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Classical Anticytokinins Do Not Interact with Cytokinin Receptors but Inhibit Cyclin-dependent Kinases
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SYSNO ASEP 0099660 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Ostatní články Title Classical Anticytokinins Do Not Interact with Cytokinin Receptors but Inhibit Cyclin-dependent Kinases Title Klasické anticytokininy neinteragují s cytokininovými receptory, ale inhibují cyklin-dependentní kinázy Author(s) Spíchal, Lukáš (UEB-Q) RID, ORCID
Kryštof, Vladimír (UEB-Q) RID, ORCID
Paprskářová, Martina (UEB-Q)
Lenobel, René (UEB-Q) ORCID
Stýskala, Jakub (UEB-Q)
Binarová, Pavla (MBU-M) RID, ORCID
Cenklová, Věra (UEB-Q)
De Veylder, L. (BE)
Inzé, D. (BE)
Kontopidis, G. (GB)
Fischer, P.M. (GB)
Schmülling, T. (DE)
Strnad, Miroslav (UEB-Q) RID, ORCIDSource Title Journal of Biological Chemistry. - : Elsevier - ISSN 0021-9258
Roč. 282, č. 19 (2007), s. 14356-14363Number of pages 8 s. Language eng - English Country US - United States Keywords Cyclin-dependent Kinases ; Anticytokinins ; Cytokinin Receptors Subject RIV EB - Genetics ; Molecular Biology R&D Projects LC06034 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) GA301/05/0418 GA ČR - Czech Science Foundation (CSF) IAA5020302 GA AV ČR - Academy of Sciences of the Czech Republic (AV ČR) GA204/07/1169 GA ČR - Czech Science Foundation (CSF) Next source Other public resourcesOther public resourcesOther public resourcesOther public resources CEZ AV0Z50380511 - UEB-Q (2005-2011) AV0Z50200510 - MBU-M (2005-2011) DOI 10.1074/jbc.M609750200 Annotation Cytokinins are a class of plant hormones that regulate the cell cycle and diverse developmental and physiological processes. Several compounds have been identified that antagonize the effects of cytokinins. Based on structural similarities and competitive inhibition, it has been assumed that these anticytokinins act through a common cellular target, namely the cytokinin receptor. Here, we examined directly the possibility that various representative classical anticytokinins inhibit the Arabidopsis cytokinin receptors CRE1/AHK4 (cytokinin response 1/Arabidopsis histidine kinase 4) and AHK3 (Arabidopsis histidine kinase 3). We show that pyrrolo[2,3-d]pyrimidine and pyrazolo[4,3-d]pyrimidine anticytokinins do not act as competitors of cytokinins at the receptor level. Flow cytometry and microscopic analyses revealed that anticytokinins inhibit the cell cycle and cause disorganization of the microtubular cytoskeleton and apoptosis. This is consistent with the hypothesis that they inhibit regulatory cyclin-dependent kinase (CDK) enzymes. Biochemical studies demonstrated inhibition by selected anti-cytokinins of both Arabidopsis and human CDKs. X-ray determination of the crystal structure of a human CDK2-anticytokinin complex demonstrated that the antagonist occupies the ATP-binding site of CDK2. Finally, treatment of human cancer cell lines with anticytokinins demonstrated their ability to kill human cells with similar effectiveness as known CDK inhibitors. Workplace Institute of Experimental Botany Contact David Klier, knihovna@ueb.cas.cz, Tel.: 220 390 469 Year of Publishing 2008
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