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

Cell Cycle. 2008 Sep 1;7(17):2691-704. doi: 10.4161/cc.7.17.6460.

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 over expression of a kinase inactive mutant revealed involvement of Aurora-A at two critical steps. These include accumulation of g-tubulin 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinase A
  • Aurora Kinases
  • Chromatin / enzymology*
  • Chromatin / ultrastructure
  • Chromosomal Proteins, Non-Histone / metabolism
  • Enzyme Activation
  • Feedback, Physiological
  • HeLa Cells
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Kinesins / metabolism
  • Kinetochores / enzymology*
  • Kinetochores / ultrastructure
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / enzymology*
  • Microtubules / ultrastructure
  • Models, Biological
  • Neoplasm Proteins / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Serine-Threonine Kinases / metabolism*
  • Spindle Apparatus / enzymology
  • Survivin
  • Tubulin / metabolism

Substances

  • BIRC5 protein, human
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • INCENP protein, human
  • Inhibitor of Apoptosis Proteins
  • KIF2C protein, human
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Survivin
  • Tubulin
  • AURKA protein, human
  • Aurora Kinase A
  • Aurora Kinases
  • Protein Serine-Threonine Kinases
  • Kinesins