A role for IκB kinase 2 in bipolar spindle assembly

Jeffrey T. Irelan, Thomas J. Murphy, Paul D. DeJesus, Hsiangling Teo, Ding Yue Xu, Maria A. Gomez-Ferreria, Yingyao Zhou, Loren J. Miraglia, Daniel R. Rines, Inder M. Verma, David J. Sharp, Vinay Tergaonkar, Sumit K. Chanda

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

IκB kinase 2 (IKK2 or IKKβ) is a component of the IKK complex that coordinates the cellular response to a diverse set of extracellular stimuli, including cytokines, microbial infection, and stress. In response to an external stimulus, the complex is activated, resulting in the phosphorylation and subsequent proteasome-mediated degradation of IκB proteins. This event triggers the nuclear import of the NF-κB transcription factor, which activates the transcription of genes that regulate a variety of fundamental biological processes, including immune response, cell survival, and development. Here, we define an essential role for IKK2 in normal mitotic progression and the maintenance of spindle bipolarity. Chemical and genetic perturbation of IKK2 promotes the formation of multipolar spindles and chromosome missegregation. Depletion of IKK2 results in the deregulation of Aurora A protein stability and coincident hyperactivation of a putative Aurora A substrate, the mitotic motor KIF11. These data support a function for IKK2 as an antagonist of Aurora A signaling during mitosis. Additionally, our results indicate a direct role for IKK2 in the maintenance of genome stability and underscore the potential for oncogenic consequences in targeting this kinase for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)16940-16945
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number43
DOIs
StatePublished - Oct 23 2007

Keywords

  • Aurora A
  • Mitosis
  • NF-κB
  • Spindle polarity

ASJC Scopus subject areas

  • General

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    Irelan, J. T., Murphy, T. J., DeJesus, P. D., Teo, H., Xu, D. Y., Gomez-Ferreria, M. A., Zhou, Y., Miraglia, L. J., Rines, D. R., Verma, I. M., Sharp, D. J., Tergaonkar, V., & Chanda, S. K. (2007). A role for IκB kinase 2 in bipolar spindle assembly. Proceedings of the National Academy of Sciences of the United States of America, 104(43), 16940-16945. https://doi.org/10.1073/pnas.0706493104