Novel E3 ligase component FBXL7 ubiquitinates and degrades Aurora A, causing mitotic arrest

Cell Cycle. 2012 Feb 15;11(4):721-9. doi: 10.4161/cc.11.4.19171. Epub 2012 Feb 15.


Aurora family kinases play pivotal roles in several steps during mitosis. Specifically, Aurora A kinase is an important regulator of bipolar mitotic spindle formation and chromosome segregation. Like other members of the Aurora family, Aurora A kinase is also regulated by post-translational modifications. Here, we show that a previously undescribed E3 ligase component belonging to the SCF (Skp-Cullin1-F-box protein) E3 ligase family, SCFFBXL7, impairs cell proliferation by mediating Aurora A polyubiquitination and degradation. Both Aurora A and FBXL7 co-localize within the centrosome during spindle formation. FBXL7 ectopic expression led to G(2)/M phase arrest in transformed epithelia, resulting in the appearance of tetraploidy and mitotic arrest with circular monopolar spindles and multipolar spindle formation. Interestingly, FBXL7 specifically interacts with Aurora A during mitosis but not in interphase, suggesting a regulatory role for FBXL7 in controlling Aurora A abundance during mitosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis / physiology
  • Aurora Kinase A
  • Aurora Kinases
  • Cell Cycle / genetics
  • Cell Cycle / physiology*
  • Cell Cycle Checkpoints / genetics
  • Cell Cycle Checkpoints / physiology*
  • Cell Line
  • Cell Line, Tumor
  • Fluorescence Resonance Energy Transfer
  • Humans
  • Mice
  • Mitosis / genetics
  • Mitosis / physiology*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • SKP Cullin F-Box Protein Ligases / genetics
  • SKP Cullin F-Box Protein Ligases / metabolism*
  • Ubiquitination / genetics
  • Ubiquitination / physiology


  • SKP Cullin F-Box Protein Ligases
  • Aurka protein, mouse
  • Aurora Kinase A
  • Aurora Kinases
  • Protein Serine-Threonine Kinases