Roscovitine Targets, Protein Kinases and Pyridoxal Kinase
 

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J. Biol. Chem. 280, 31208-31219.
 

 Bach, S., Knockaert, M., Lozach, O., Reinhardt, J., Baratte, B., Schmitt, S., Coburn, S.P., Tang, L., Jiang. T., Liang, D.C., Galons, H., Dierick, J.F., Totzke, F., Sch├Ąchtele, C., Lerman, A.S., Carnero, A., Wan, Y., Gray, N. and Meijer, L.
 

Correspondence: Laurent Meijer
 Tel.: 33-0-2-98-29-23-39; Fax: 33-0-2-98-29-23-42; E-mail:
Prof. Laurent Meijer


(R)-Roscovitine (CYC202) is often referred to as a "selective inhibitor of cyclin-dependent kinases." Besides its use as a biological tool in cell cycle, neuronal functions, and apoptosis studies, it is currently evaluated as a potential drug to treat cancers, neurodegenerative diseases, viral infections, and glomerulonephritis. We have investigated the selectivity of (R)-roscovitine using three different methods: 1) testing on a wide panel of purified kinases that, along with previously published data, now reaches 151 kinases; 2) identifying roscovitine-binding proteins from various tissue and cell types following their affinity chromatography purification on immobilized roscovitine; 3) investigating the effects of roscovitine on cells deprived of one of its targets, CDK2. Altogether, the results show that (R)-roscovitine is rather selective for CDKs, in fact most kinases are not affected. However, it binds an unexpected, non-protein kinase target, pyridoxal kinase, the enzyme responsible for phosphorylation and activation of vitamin B6. These results could help in interpreting the cellular actions of (R)-roscovitine but also in guiding the synthesis of more selective roscovitine analogs.

 

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