期刊
MOLECULAR CANCER
卷 12, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1476-4598-12-4
关键词
Clathrin; Pitstop; Spindle assembly checkpoint; Metaphase; Cell death; Cancer
资金
- National Health and Medical Research Council (NH&MRC) of Australia
- NH&MRC Career Development Award Fellowship
- German funding agency DFG [SFB765/B4, FOR806-HA2686/3-2]
Background: During metaphase clathrin stabilises the mitotic spindle kinetochore(K)-fibres. Many anti-mitotic compounds target microtubule dynamics. Pitstop 2 (TM) is the first small molecule inhibitor of clathrin terminal domain and inhibits clathrin-mediated endocytosis. We investigated its effects on a second function for clathrin in mitosis. Results: Pitstop 2 did not impair clathrin recruitment to the spindle but disrupted its function once stationed there. Pitstop 2 trapped HeLa cells in metaphase through loss of mitotic spindle integrity and activation of the spindle assembly checkpoint, phenocopying clathrin depletion and aurora A kinase inhibition. Conclusions: Pitstop 2 is therefore a new tool for investigating clathrin spindle dynamics. Pitstop 2 reduced viability in dividing HeLa cells, without affecting dividing non-cancerous NIH3T3 cells, suggesting that clathrin is a possible novel anti-mitotic drug target.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据