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

Volume 11, Issue 4   February 15, 2012
Pages 721 - 729
http://dx.doi.org/10.4161/cc.11.4.19171
Authors: Tiffany A. Coon, Jennifer R. Glasser, Rama K. Mallampalli and Bill B. Chen

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Abstract:
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 G2/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.

Received: October 24, 2011; Accepted: December 23, 2011

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