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 language | English (US) |
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Pages (from-to) | 2691-2704 |
Number of pages | 14 |
Journal | Cell Cycle |
Volume | 7 |
Issue number | 17 |
DOIs | |
State | Published - Sep 1 2008 |
Keywords
- Aurora-A
- Centrosome
- INCENP
- Kinetochore associated microtubule formation
- Phosphorylation
ASJC Scopus subject areas
- Cell Biology
- Biochemistry
- Molecular Biology