Overexpression of mitotic centromere-associated Kinesin stimulates microtubule detachment and confers resistance to paclitaxel.

ABSTRACT: Numerous studies have implicated mutations in tubulin or the overexpression of specific tubulin genes in resistance to microtubule-targeted drugs. Much less is known about the role of accessory proteins that modulate microtubule behavior in the genesis of drug resistance. Here, we examine mitotic centromere-associated kinesin (MCAK), a member of the kinesin family of microtubule motor proteins that has the ability to stimulate microtubule depolymerization, and show that overexpressing the protein confers resistance to paclitaxel and epothilone A, but increases sensitivity to colcemid. Cells transfected with FLAG-tagged MCAK cDNA using a tet-off-regulated expression system had a disrupted microtubule cytoskeleton and were able to survive a toxic concentration of paclitaxel in the absence, b

SUBMITTER: Ganguly A 

PROVIDER: S-EPMC3112244 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature