A functional genomic screen identifies a role for TAO1 kinase in spindle-checkpoint signalling

Viji M. Draviam, Frank Stegmeier, Grzegorz Nalepa, Mathew E. Sowa, Jing Chen, Anthony Liang, Gregory J. Hannon, Peter K. Sorger, J. Wade Harper, Stephen J. Elledge

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Abstract

Defects in chromosome-microtubule attachment trigger spindle-checkpoint activation and delay mitotic progression. How microtubule attachment is sensed and integrated into the steps of checkpoint-signal amplification is poorly understood. In a functional genomic screen targeting human kinases and phosphatases, we identified a microtubule affinity-regulating kinase kinase, TAO1 (also known as MARKK) as an important regulator of mitotic progression, required for both chromosome congression and checkpoint-induced anaphase delay. TAO1 interacts with the checkpoint kinase BubR1 and promotes enrichment of the checkpoint protein Mad2 at sites of defective attachment, providing evidence for a regulatory step that precedes the proposed Mad2-Mad1 dependent checkpoint-signal amplification step. We propose that the dual functions of TAO1 in regulating microtubule dynamics and checkpoint signalling may help to coordinate the establishment and monitoring of correct congression of chromosomes, thereby protecting genomic stability in human cells.

Original languageEnglish (US)
Pages (from-to)556-564
Number of pages9
JournalNature Cell Biology
Volume9
Issue number5
DOIs
StatePublished - May 1 2007

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ASJC Scopus subject areas

  • Cell Biology

Cite this

Draviam, V. M., Stegmeier, F., Nalepa, G., Sowa, M. E., Chen, J., Liang, A., Hannon, G. J., Sorger, P. K., Harper, J. W., & Elledge, S. J. (2007). A functional genomic screen identifies a role for TAO1 kinase in spindle-checkpoint signalling. Nature Cell Biology, 9(5), 556-564. https://doi.org/10.1038/ncb1569