Aurora kinase-A regulates kinetochore/chromatin associated microtubule assembly in human cells

Hiroshi Katayama, Kaori Sasai, Malgorzata Kloc, Bill R. Brinkley, Subrata Sen

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

Microtubule nucleation and formation from the kinetochore/chromatin have been proposed to contribute to bipolar spindle assembly facilitating equal segregation of chromosomes in mitosis. Although two independent pathways involving the small Ran GTPase-TPX2 proteins and the chromosomal passenger complex proteins have been implicated in the formation of microtubules from the kinetochore/chromatin, detailed molecular mechanisms integrating the pathways and regulating the process have not been well elucidated. This study demonstrates that Aurora kinase-A plays a central role in the kinetochore/chromatin associated microtubule assembly in human cells by integrating the two pathways regulating the process. Silencing by siRNA and overexpression of a kinase inactive mutant revealed involvement of Aurora-A at two critical steps. These include formation of ?-tubulin foci in the vicinity of kinetochore/chromatin to create microtubule nucleation sites as well as INCENP and TPX2 mediated activation of Aurora-A facilitating formation and stabilization of microtubules. The findings provide the first evidence of Aurora-A, in association with INCENP and TPX2, being a key regulator of kinetochore/chromatin associated microtubule formation in human cells.

Original languageEnglish
Pages (from-to)2691-2704
Number of pages14
JournalCell Cycle
Volume7
Issue number17
DOIs
Publication statusPublished - Sep 1 2008

Keywords

  • Aurora-A
  • Centrosome
  • INCENP
  • Kinetochore associated microtubule formation
  • Phosphorylation

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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