Novel E3 ligase component FBXL7 ubiquitinates and degrades Aurora A,causing mitotic arrest |
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| Authors: | Tiffany A Coon Jennifer R Glasser Rama K Mallampalli Bill B Chen |
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| Institution: | 1.Department of Medicine; Acute Lung Injury Center of Excellence; University of Pittsburgh; Pittsburgh, PA USA;2.Department of Cell Biology and Physiology; University of Pittsburgh; Pittsburgh, PA USA;3.Medical Specialty Service Line; Veterans Affairs Pittsburgh Healthcare System; Pittsburgh, PA USA |
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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.Key words: F-box protein, centrosome, mitosis, Aurora A |
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