In:
Molecular Cancer, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2013-12)
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1476-4598
DOI:
10.1186/1476-4598-12-4
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2013
detail.hit.zdb_id:
2091373-4
