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

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

Author information

1
Department of Medicine, Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA.

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 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.

PMID:
22306998
PMCID:
PMC3318106
DOI:
10.4161/cc.11.4.19171
[Indexed for MEDLINE]
Free PMC Article

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