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Aurora A, MCAK, and Kif18b promote Eg5-independent spindle formation

Roy G H P van Heesbeen1, Jonne A Raaijmakers1, Marvin E Tanenbaum2

  • 1Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Chromosoma
|June 30, 2016
PubMed

Insights

Eg5 inhibitors can be resisted by Eg5-independent pathways. This study identifies Aurora A, MCAK, and Kif18b as essential for bipolar spindle formation in Eg5-independent cells, revealing new anti-cancer targets.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Eg5 motor protein inhibition causes monopolar spindles, a target for cancer therapy.
  • Eg5-independent pathways can lead to resistance against Eg5 inhibitors.
  • Understanding Eg5-independent bipolar spindle formation is crucial for overcoming treatment resistance.

Purpose of the Study:

  • To identify essential components for Eg5-independent bipolar spindle formation.
  • To elucidate mechanisms by which Eg5-independent cells assemble bipolar spindles.
  • To discover novel targets for anti-cancer therapies that overcome Eg5 inhibitor resistance.

Main Methods:

  • Genome-wide siRNA screen in Eg5-independent cells (EICs).
  • Analysis of essential proteins for bipolar spindle assembly.
  • Investigation of kinase and kinesin roles in microtubule dynamics and spindle formation.

Main Results:

  • Aurora A, MCAK, and Kif18b are essential for bipolar spindle assembly in EICs and cells with reduced Eg5 activity.
  • Aurora A promotes bipolar spindle assembly via Kif15 phosphorylation and localization.
  • MCAK and Kif18b promote bipolar spindle assembly by destabilizing astral microtubules.

Conclusions:

  • Astral microtubules play a novel role in force generation on spindle poles.
  • Regulators of microtubule length are critical for bipolar spindle assembly.
  • Identified proteins offer potential targets to enhance anti-cancer therapies by inhibiting Eg5-independent pathways.
Keywords:
Aurora AEg5Kif15Kif18BMCAKSpindle

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