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Selective Small-Molecule Inhibitor Reveals Critical Mitotic Functions of Human CDK1
CDK1 is a nonredundant cyclin-dependent kinase (CDK) with an essential role in mitosis, but its multiple functions still are poorly understood at a molecular level. Here we identify a selective small-molecule inhibitor of CDK1 that reversibly arrests human cells at the G₂/M border of the cell cycle...
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| Published in: | Proceedings of the National Academy of Sciences - PNAS 2006-07, Vol.103 (28), p.10660-10665 |
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| Main Authors: | , , , , , , , |
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| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-c565t-81830e769924518fd3a922198f5e2c1ef64c306a6f7ef855cc1fe81bff51f45d3 |
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| cites | cdi_FETCH-LOGICAL-c565t-81830e769924518fd3a922198f5e2c1ef64c306a6f7ef855cc1fe81bff51f45d3 |
| container_end_page | 10665 |
| container_issue | 28 |
| container_start_page | 10660 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 103 |
| creator | Vassilev, Lyubomir T. Tovar, Christian Chen, Shaoqing Knezevic, Dejan Zhao, Xiaolan Sun, Hongmao Heimbrook, David C. Chen, Li |
| description | CDK1 is a nonredundant cyclin-dependent kinase (CDK) with an essential role in mitosis, but its multiple functions still are poorly understood at a molecular level. Here we identify a selective small-molecule inhibitor of CDK1 that reversibly arrests human cells at the G₂/M border of the cell cycle and allows for effective cell synchronization in early mitosis. Inhibition of CDK1 during cell division revealed that its activity is necessary and sufficient for maintaining the mitotic state of the cells, preventing replication origin licensing and premature cytokinesis. Although CDK1 inhibition for up to 24 h is well tolerated, longer exposure to the inhibitor induces apoptosis in tumor cells, suggesting that selective CDK1 inhibitors may have utility in cancer therapy. |
| doi_str_mv | 10.1073/pnas.0600447103 |
| format | article |
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| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2006-07, Vol.103 (28), p.10660-10665 |
| issn | 0027-8424 1091-6490 |
| language | eng |
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| source | JSTOR Archival Journals and Primary Sources Collection; PubMed Central |
| subjects | Apoptosis Apoptosis - drug effects Apoptosis - physiology Biological Sciences Catalysis CDC2 Protein Kinase - antagonists & inhibitors CDC2 Protein Kinase - physiology Cell cycle Cell growth Cell Line, Tumor Cell lines Cell Proliferation - drug effects Chromatin Cyclin-dependent kinases Cyclins Enzyme Inhibitors - pharmacology Epithelial cells HCT116 Cells HeLa Cells Humans Interphase Mitosis Mitosis - drug effects Mitosis - physiology Quinolines - pharmacology Radiation therapy Studies Thiazoles - pharmacology |
| title | Selective Small-Molecule Inhibitor Reveals Critical Mitotic Functions of Human CDK1 |
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