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Journal Articles Journal of Biological Chemistry Year : 2005

Roscovitine Targets, Protein Kinases and Pyridoxal Kinase

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Jean-Francois Dierick
  • Function : Author
Frank Totzke
  • Function : Author
Christoph Schächtele
  • Function : Author

Abstract

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 B 6. 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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Dates and versions

hal-03867064 , version 1 (23-11-2022)

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Stéphane Bach, Marie Knockaert, Jens Reinhardt, Olivier Lozach, Sophie Schmitt, et al.. Roscovitine Targets, Protein Kinases and Pyridoxal Kinase. Journal of Biological Chemistry, 2005, 280, pp.31208 - 31219. ⟨10.1074/jbc.m500806200⟩. ⟨hal-03867064⟩
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