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Kinesin-5 mitotic motors: is loop5 the on/off switch?

Moores, Carolyn A. (2010) Kinesin-5 mitotic motors: is loop5 the on/off switch? Cell Cycle 9 (7), pp. 1286-1290. ISSN 1551-4005.

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Official URL: http://dx.doi.org/10.4161/cc.9.7.11144

Abstract

The microtubule-based mitotic spindle orchestrates chromosome segregation, facilitated by many microtubule-associated proteins. Kinesin-5 proteins are important components of the cell division machinery, and are involved in generation of mitotic spindle bipolarity by cross-linking microtubules. Kinesin-5s are members of the ATP- and MT-dependent kinesin superfamily of molecular motors. Human kinesin-5 is also a target for small molecule inhibitors that specifically bind to the motor domain and are currently in cancer clinical trials. The regulatory mechanisms that control kinesin-5 activity during mitosis and the effects of regulation on the kinesin-5-microtubule interaction remain unknown. Recent work has focused on a kinesin-5 specific region within the motor domain, loop5, as a potential regulatory switch. Kinesin-5-specific small molecule inhibitors bind beneath loop5, loop5 is rearranged when kinesin-5 binds to microtubules and residues adjacent to loop5 are subject to cell cycle-dependent tyrosine phosphorylation which could affect its conformation. It will be essential to consider these studies, which shed light on potential kinesin-5 regulatory mechanisms, as part of efforts to develop clinically effective kinesin-5 inhibitors.

Item Type: Article
Additional Information: Available via Gold Open Access at official URL
Keyword(s) / Subject(s): kinesin, microtubule, mitosis, cancer, spindle, KSP, monastrol, Wee1
School or Research Centre: Birkbeck Schools and Research Centres > School of Science > Biological Sciences
Depositing User: Administrator
Date Deposited: 04 Aug 2010 14:09
Last Modified: 17 Apr 2013 12:17
URI: http://eprints.bbk.ac.uk/id/eprint/1043

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