%0 Journal Article
%T Inhibition of clathrin by pitstop 2 activates the spindle assembly checkpoint and induces cell death in dividing HeLa cancer cells
%A Smith Charlotte M
%A Haucke Volker
%A McCluskey Adam
%A Robinson Phillip J
%J Molecular Cancer
%D 2013
%I BioMed Central
%R 10.1186/1476-4598-12-4
%X 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.
%K Clathrin
%K Pitstop
%K Spindle assembly checkpoint
%K Metaphase
%K Cell death
%K Cancer
%U http://www.molecular-cancer.com/content/12/1/4