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Aurora-A and ch-TOG act in a common pathway in control of spindle pole integrity

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Abstract

Mitotic spindle assembly is a highly regulated process, crucial to ensure the correct segregation of duplicated chromosomes in daughter cells and to avoid aneuploidy, a common feature of tumors. Among the most important spindle regulators is Aurora-A, a mitotic centrosomal kinase frequently overexpressed in tumors. Here, we investigated the role of Aurora-A in spindle pole organization in human cells. We show that RNA interference-mediated Aurora-A inactivation causes pericentriolar material fragmentation in prometaphase, yielding the formation of spindles with supernumerary poles. This fragmentation does not necessarily involve centrioles and requires microtubules (MTs). Aurora-A-depleted prometaphases mislocalize the MT-stabilizing protein colonic hepatic tumor-overexpressed gene (ch-TOG), which abnormally accumulates at spindle poles, as well as the mitotic centromere-associated kinesin (MCAK), the major functional antagonist of ch-TOG, which delocalizes from poles. ch-TOG is required for extrapole formation in prometaphases lacking Aurora-A, because co-depletion of Aurora-A and ch-TOG mitigates the fragmented pole phenotype. These results indicate a novel function of Aurora-A, the regulation of ch-TOG and MCAK localization, and highlight a common pathway involving the three factors in control of spindle pole integrity.

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Acknowledgements

We thank M Ciciarello and R Mangiacasale for helpful discussions and JL Salisbury and C Walczak for reagents. This work was supported by AIRC (Italian Association for Cancer Research) grants (to PL).

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Authors and Affiliations

  1. Institute of Molecular Biology and Pathology, CNR, c/o University of Rome ‘La Sapienza’, Rome, Italy

    M De Luca, L Brunetto, I A Asteriti, M Giubettini, P Lavia & G Guarguaglini

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  1. M De Luca
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  2. L Brunetto
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  3. I A Asteriti
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  4. M Giubettini
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  5. P Lavia
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  6. G Guarguaglini
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Corresponding author

Correspondence to G Guarguaglini.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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De Luca, M., Brunetto, L., Asteriti, I. et al. Aurora-A and ch-TOG act in a common pathway in control of spindle pole integrity. Oncogene 27, 6539–6549 (2008). https://doi.org/10.1038/onc.2008.252

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  • DOI: https://doi.org/10.1038/onc.2008.252

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