- Title
- Inhibition of clathrin by pitstop 2 activates the spindle assembly checkpoint and induces cell death in dividing HeLa cancer cells
- Creator
- Smith, Charlotte M.; Haucke, Volker; McCluskey, Adam; Robinson, Phillip J.; Chircop, Megan
- Relation
- Molecular Cancer Vol. 12
- Publisher Link
- http://dx.doi.org/10.1186/1476-4598-12-4
- Publisher
- Biomed Central
- Resource Type
- journal article
- Date
- 2013
- Description
- Background: During metaphase clathrin stabilises the mitotic spindle kinetochore(K)-fibres. Many anti-mitotic compounds target microtubule dynamics. Pitstop 2™ 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.
- Subject
- clathrin; pitstop; spindle assembly checkpoint; metaphase; cell death; cancer
- Identifier
- http://hdl.handle.net/1959.13/1300473
- Identifier
- uon:20085
- Identifier
- ISSN:1476-4598
- Language
- eng
- Full Text
- Reviewed
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