Classical Anticytokinins Do Not Interact with Cytokinin Receptors but Inhibit Cyclin-dependent Kinases

Spíchal, Lukáš; Kryštof, Vladimír; Paprskářová, Martina; Lenobel, René; Stýskala, Jakub; Binarová, Pavla; Cenklová, Věra; De Veylder, L.; Inzé, D.; Kontopidis, G.; Fischer, P.M.; Schmülling, T.; Strnad, Miroslav

doi:https://dx.doi.org/10.1074/jbc.M609750200

Number of the records: 1

Classical Anticytokinins Do Not Interact with Cytokinin Receptors but Inhibit Cyclin-dependent Kinases

1.

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, ORCID}
Source Title	Journal of Biological Chemistry. - : Elsevier - ISSN 0021-9258 Roč. 282, č. 19 (2007), s. 14356-14363
Number 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

Number of the records: 1