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KMID : 0578319960060060679
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Molecules and Cells
1996 Volume.6 No. 6 p.679 ~ p.683
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A specific Inhibitor of Cyclin-dependent Protein Kinases, CDC2 and CDK2
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Park, Sang gon
Cheon, Je young/Lee, Yong Hee/Park, Joo-Seop/Lee, Kwang Youl/Lee, Chul hoon/Lee, Seung Ki
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Abstract
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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 (C_(12)H_(13)N_(5)O_(4),M_(r) 291.266). To determine whether toyocamycin is able to specifically inhibit cyclin dependent kinase (CDK) family kinase activity, a histone Hl kinase assay was peformed 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 IC_(50) value of 0.88 μM. This nucleoside antibiotic also inhibited immunoprecipitated CDK2 kinase activity with an IC_(50) 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.
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