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J Cell Sci 2008 Jul 15;121Pt 14:2293-300. doi: 10.1242/jcs.024018.
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A novel small-molecule inhibitor reveals a possible role of kinesin-5 in anastral spindle-pole assembly.

Groen AC , Needleman D , Brangwynne C , Gradinaru C , Fowler B , Mazitschek R , Mitchison TJ .

The tetrameric plus-end-directed motor, kinesin-5, is essential for bipolar spindle assembly. Small-molecule inhibitors of kinesin-5 have been important tools for investigating its function, and some are currently under evaluation as anti-cancer drugs. Most inhibitors reported to date are ;non-competitive' and bind to a specific site on the motor head, trapping the motor in an ADP-bound state in which it has a weak but non-zero affinity for microtubules. Here, we used a novel ATP-competitive inhibitor, FCPT, developed at Merck (USA). We found that it induced tight binding of kinesin-5 onto microtubules in vitro. Using Xenopus egg-extract spindles, we found that FCPT not only blocked poleward microtubule sliding but also selectively induced loss of microtubules at the poles of bipolar spindles (and not asters or monoasters). We also found that the spindle-pole proteins TPX2 and gamma-tubulin became redistributed to the spindle equator, suggesting that proper kinesin-5 function is required for pole assembly.

PubMed ID: 18559893
PMC ID: PMC2902979
Article link: J Cell Sci
Grant support: [+]

Species referenced: Xenopus
Genes referenced: tpx2 tubg1

References [+] :
Brier, Identification of the protein binding region of S-trityl-L-cysteine, a new potent inhibitor of the mitotic kinesin Eg5. 2004, Pubmed