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A role for IkappaB kinase 2 in bipolar spindle assembly.

IkappaB kinase 2 (IKK2 or IKKbeta) 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 IkappaB proteins. This event triggers the nuclear import of the NF-kappaB 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.

Pubmed ID: 17939994

Authors

  • Irelan JT
  • Murphy TJ
  • DeJesus PD
  • Teo H
  • Xu D
  • Gomez-Ferreria MA
  • Zhou Y
  • Miraglia LJ
  • Rines DR
  • Verma IM
  • Sharp DJ
  • Tergaonkar V
  • Chanda SK

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

October 23, 2007

Associated Grants

None

Mesh Terms

  • Aneuploidy
  • Animals
  • Aurora Kinase A
  • Aurora Kinases
  • Cell Cycle
  • Cell Polarity
  • Cell Transformation, Neoplastic
  • Enzyme Inhibitors
  • Fibroblasts
  • HeLa Cells
  • Humans
  • I-kappa B Kinase
  • Mice
  • Mice, Nude
  • Protein-Serine-Threonine Kinases
  • RNA, Small Interfering
  • Signal Transduction
  • Spindle Apparatus