Abstract:
:We screened cdc2 kinase inhibitors from cultured mediums of micro organisms using purified mouse cyclin B-cdc2 kinase and a specific substrate peptide for cdc2 kinase. A selective inhibitor of cdc2 kinase was isolated from the cultured medium of Aspergillus species F-25799, and identified as butyrolactone I. Butyrolactone I inhibited cdc2 and cdk2 kinases but it had little effect on mitogen-activated protein kinase, protein kinase C, cyclic-AMP dependent kinase, casein kinase II, casein kinase I or epidermal growth factor-receptor tyrosine kinase. Its inhibitory effect was found to be due to competition with ATP. Butyrolactone I selectively inhibited the H1 histone phosphorylation in nuclear extracts. It also inhibited the phosphorylation of the product of retinoblastoma susceptibility gene in nuclear extracts and intact cells. Thus butyrolactone I should be very useful for elucidating the function of cdc2 and cdk2 kinases in cell cycle regulation.
journal_name
Oncogenejournal_title
Oncogeneauthors
Kitagawa M,Okabe T,Ogino H,Matsumoto H,Suzuki-Takahashi I,Kokubo T,Higashi H,Saitoh S,Taya Y,Yasuda Hsubject
Has Abstract,Author List Incompletepub_date
1993-09-01 00:00:00pages
2425-32issue
9eissn
0950-9232issn
1476-5594journal_volume
8pub_type
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