A specific inhibitor of cyclin-dependent protein kinases, CDC2 and CDK2

Sang Gon Park, Je Young Cheon, Yong Hee Lee, Joo Seop Park, Kwang Youl Lee, Chul Hoon Lee, Seung Ki Lee*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

We screened cyclin-dependent protein kinase inhibitors from culture media of soil microorganisms by in vitro enzyme assay system using a specific synthetic peptide substrate, CSH103. A selective and very potent inhibitor of CDC2 kinase activity was isolated from the culture medium of Streptomyces sp. LPL931 and identified as toyocamycin (C12H13N5O4, Mr 291.266). To determine whether toyocamycin is able to specifically inhibit cyclin dependent kinase (CDK) family kinase activity, a histone H1 kinase assay was performed with immunoprecipitates of CDC2 or CDK2 using specific antibodies. The result showed that toyocamycin competitively inhibits immunoprecipitated CDC2 kinase activity with a Ki value of 1.55 μM against ATP and an IC50 value of 0.88 μM. This nucleoside antibiotic also inhibited immunoprecipitated CDK2 kinase activity with an IC50 value of about 1 μM, but inhibited less effectively other kinases tested. Furthermore, MTT assay revealed that the agent is able to suppress cell proliferation of Sk-Hep-1 cells at a concentration of 1-10 μM.

Original languageEnglish (US)
Pages (from-to)679-683
Number of pages5
JournalMolecules and Cells
Volume6
Issue number6
StatePublished - Dec 31 1996

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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