| Ubiquitin specific protease 7 deubiquitinates and regulates Aurora B-mediated cytokinesis |
Kamini Kaushal1 (Student), Ainsley Mike Antao1,# (Student), Soumyadip Das1,# (Student), Sammy L. Kim2,# (Student), Girish Birappa1 (Student), Sripriya Rajkumar1 (Student), D.A. Ayush Gowda1 (Student), C. Bindu Ajaykumar1 (Student), Vijai Singh3 (Professor), Keesung Kim4 (Research Professor), Bharathi Suresh1 (Research Professor), Suresh Ramakrishna  1,5,* (Professor) |
1Department of Biomedical Science and Engineering, Hanyang University,
2Department of Biological Science, Konkuk University,
3Department of Biosciences, Indrashil University,
4Research Institute of Advanced Materials, Seoul National University,
5College of Medicine, Hanyang University |
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Abstract
Aurora B is a widely studied mitotic checkpoint kinase that forms a part of the chromosomal passenger complex. The entry to and exit from mitosis are exquisitely controlled by Aurora B proteins, which regulate mitotic phases including chromosomal condensation, segregation, and cytokinesis, ensuring faithful propagation of daughter cells. Abnormal regulation of Aurora B proteins during the cell cycle can cause increased chromosomal segregation errors and ultimately lead to cancer. Thus, it is important to understand the key mechanisms that can modulate Aurora B protein levels during the cell cycle. Therefore, in this study we demonstrated the role of Ubiquitin-specific protease 7 (USP7) in regulating Aurora B protein level. Aurora B protein levels are upregulated when USP7 is dose-dependently increased, and downregulated when USP7 is depleted. By co-immunoprecipitation and Duolink assays, we demonstrated that USP7 interact with Aurora B. Furthermore, by treating cycloheximide we showed that USP7 extends the Aurora B protein half-life by its deubiquitinating activity. Finally, CRISPR/Cas9-mediated USP7 knockout produces severe nuclear structural defects causing multi-nucleation and cytokinesis failures, suggesting that the important role of USP7 during mitotic progression in stabilizing Aurora B.
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| Abstract, Accepted Manuscript [Submitted on October 8, 2024, Accepted on November 15, 2024] |
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