期刊
NATURE COMMUNICATIONS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms9722
关键词
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资金
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- Japan Society for the Promotion of Science (JSPS) [23390029, 24659092, 25113723, 25293046]
- Deutsche Forschungsgemeinschaft [Schi295/4-2]
- Uehara memorial foundation
- JSPS
- Special Postdoctoral Researcher (SPDR) programme in RIKEN
- Grants-in-Aid for Scientific Research [25113723, 25293046, 24659092, 25350960] Funding Source: KAKEN
Inhibitors of microtubule (MT) assembly or dynamics that target alpha/beta-tubulin are widely exploited in cancer therapy and biological research. However, specific inhibitors of the MT nucleator gamma-tubulin that would allow testing temporal functions of g-tubulin during the cell cycle are yet to be identified. By evolving beta-tubulin-binding drugs we now find that the glaziovianin A derivative gatastatin is a gamma-tubulin-specific inhibitor. Gatastatin decreased interphase MT dynamics of human cells without affecting MT number. Gatastatin inhibited assembly of the mitotic spindle in prometaphase. Addition of gatastatin to preformed metaphase spindles altered MT dynamics, reduced the number of growing MTs and shortened spindle length. Furthermore, gatastatin prolonged anaphase duration by affecting anaphase spindle structure, indicating the continuous requirement of MT nucleation during mitosis. Thus, gatastatin facilitates the dissection of the role of gamma-tubulin during the cell cycle and reveals the sustained role of gamma-tubulin.
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