Ubiquitin specific protease 7 deubiquitinates and regulates Aurora B-mediated cytokinesis
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Aurora B is a widely studied mitotic checkpoint kinase thatforms a part of the chromosomal passenger complex. Theentry to and exit from mitosis are exquisitely controlled byAurora B proteins, which regulate mitotic phases includingchromosomal condensation, segregation, and cytokinesis, ensuringfaithful propagation of daughter cells. Abnormal regulationof Aurora B proteins during the cell cycle can causeincreased chromosomal segregation errors and ultimately leadto cancer. Thus, it is important to understand the key mechanismsthat can modulate Aurora B protein levels during thecell cycle. Therefore, in this study we demonstrated the role ofUbiquitin-specific protease 7 (USP7) in regulating Aurora Bprotein level. Aurora B protein levels are upregulated whenUSP7 is dose-dependently increased, and downregulated whenUSP7 is depleted. By co-immunoprecipitation and Duolinkassays, we demonstrated that USP7 interact with Aurora B. Furthermore, by treating cycloheximide we showed that USP7extends the Aurora B protein half-life by its deubiquitinatingactivity. Finally, CRISPR/Cas9-mediated USP7 knockout producessevere nuclear structural defects causing multi-nucleation andcytokinesis failures, suggesting that the important role of USP7during mitotic progression in stabilizing Aurora B.
Abstract
Aurora B is a widely studied mitotic checkpoint kinase thatforms a part of the chromosomal passenger complex. Theentry to and exit from mitosis are exquisitely controlled byAurora B proteins, which regulate mitotic phases includingchromosomal condensation, segregation, and cytokinesis, ensuringfaithful propagation of daughter cells. Abnormal regulationof Aurora B proteins during the cell cycle can causeincreased chromosomal segregation errors and ultimately leadto cancer. Thus, it is important to understand the key mechanismsthat can modulate Aurora B protein levels during thecell cycle. Therefore, in this study we demonstrated the role ofUbiquitin-specific protease 7 (USP7) in regulating Aurora Bprotein level. Aurora B protein levels are upregulated whenUSP7 is dose-dependently increased, and downregulated whenUSP7 is depleted. By co-immunoprecipitation and Duolinkassays, we demonstrated that USP7 interact with Aurora B. Furthermore, by treating cycloheximide we showed that USP7extends the Aurora B protein half-life by its deubiquitinatingactivity. Finally, CRISPR/Cas9-mediated USP7 knockout producessevere nuclear structural defects causing multi-nucleation andcytokinesis failures, suggesting that the important role of USP7during mitotic progression in stabilizing Aurora B.