Title

Kinesin-5: Cross-Bridging Mechanism to Targeted Clinical Therapy.

Funding Source

National Institutes of Health

Grant Number

R01GM097350,5G12RR026260,R01GM066328,P20GM103424

Department

Department of Biology

Document Type

Article

Publication Date

12-1-2013

Abstract

Kinesin motor proteins comprise an ATPase superfamily that works hand in hand with microtubules in every eukaryote. The mitotic kinesins, by virtue of their potential therapeutic role in cancerous cells, have been a major focus of research for the past 28. years since the discovery of the canonical Kinesin-1 heavy chain. Perhaps the simplest player in mitotic spindle assembly, Kinesin-5 (also known as Kif11, Eg5, or kinesin spindle protein, KSP) is a plus-end-directed motor localized to interpolar spindle microtubules and to the spindle poles. Comprised of a homotetramer complex, its function primarily is to slide anti-parallel microtubules apart from one another. Based on multi-faceted analyses of this motor from numerous laboratories over the years, we have learned a great deal about the function of this motor at the atomic level for catalysis and as an integrated element of the cytoskeleton. These data have, in turn, informed the function of motile kinesins on the whole, as well as spearheaded integrative models of the mitotic apparatus in particular and regulation of the microtubule cytoskeleton in general. We review what is known about how this nanomotor works, its place inside the cytoskeleton of cells, and its small-molecule inhibitors that provide a toolbox for understanding motor function and for anticancer treatment in the clinic.

Comments

DOI: 10.1016/j.gene.2013.08.004

PubMed ID: 23954229

Funding text

We thank members of the Huckaba, Kim, Wojcik, and Worthylake laboratories for their intellectual input and criticism. This work was funded by grants from the National Institutes of Health ( R01GM097350 to S.K.; R01GM066328 to E.W.; and P20GM103424 and 5G12RR026260 to T.H.) and the School of Graduate Studies at LSU Health Sciences Center — New Orleans (R.B. and J.R.).

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