Effects of anti-microtubule agents on microtubule organization in cells lacking the kinesin-13 MCAK

David G. Hedrick, Jane R. Stout, Claire Walczak

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Dynamic microtubules are necessary for proper mitotic spindle assembly and chromosome segregation during mitosis. Members of the kinesin superfamily of molecular motor proteins are important to spindle function. Of particular interest is the Kinesin-13 family member MCAK, which acts to regulate microtubule dynamics during spindle assembly and to ensure proper attachments of chromosomes to spindle microtubules. The unique ability of MCAK to regulate microtubule dynamics makes it a potential target for development of new drugs that alter spindle function. Here, we knocked down MCAK via RNAi in normal and malignant cell lines and found that the two tested malignant cell lines were acutely sensitive to MCAK knockdown, while the tested normal cells were less sensitive. In addition, we looked at the effect of combining MCAK knockdown and drug treatment with paclitaxel or vinblas-tine to identify spindle assembly defects. We found that MCAK knockdown increased the morphological defects of the microtubule cytoskeleton in HeLa cells caused by anti-microtubule drugs. Our studies support the idea that MCAK would be a good target for new chemotherapeutic development and may be particularly useful in combination therapies with currently available anti-microtubule agents.

Original languageEnglish
Pages (from-to)2146-2156
Number of pages11
JournalCell Cycle
Volume7
Issue number14
StatePublished - Jul 15 2008

Fingerprint

Kinesin
Microtubules
Chromosomes
Molecular Motor Proteins
Cells
Drug therapy
Defects
Paclitaxel
Pharmaceutical Preparations
Cell Line
Chromosome Segregation
Spindle Apparatus
Aptitude
RNA Interference
Cytoskeleton
HeLa Cells
Mitosis

Keywords

  • Cell cycle
  • Chemotherapeutic target
  • Kinesins
  • Microtubule dynamics
  • Mitosis

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Cite this

Effects of anti-microtubule agents on microtubule organization in cells lacking the kinesin-13 MCAK. / Hedrick, David G.; Stout, Jane R.; Walczak, Claire.

In: Cell Cycle, Vol. 7, No. 14, 15.07.2008, p. 2146-2156.

Research output: Contribution to journalArticle

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