Proceedings of the National Academy of Sciences - PNAS, 2006-07, Vol.103 (28), p.10660-10665
2006
Details
- Autor(en) / Beteiligte
- Titel
- Selective Small-Molecule Inhibitor Reveals Critical Mitotic Functions of Human CDK1
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2006-07, Vol.103 (28), p.10660-10665
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2006
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.0600447103Titel-ID: cdi_proquest_miscellaneous_17262158
- Format
- –
- Schlagworte
- 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