OTUD6A Is an AURORA Kinase A-Specific Deubiquitinase

• Main Authors: Hyo Jin Kim, Jongchan Kim
• Format: Article
• Language: English
• Published: MDPI AG 2021-02-01
• Series: International Journal of Molecular Sciences
• Subjects: Aurora kinase A; cancer; deubiquitinase; OTUD6A
• Online Access: https://www.mdpi.com/1422-0067/22/4/1936

Aurora kinases are serine/threonine kinases required for cell proliferation and are overexpressed in many human cancers. Targeting Aurora kinases has been a therapeutic strategy in cancer treatment. Here, we attempted to identify a deubiquitinase (DUB) that regulates Aurora kinase A (Aurora-A) protein stability and/or kinase activity as a potential cancer therapeutic target. Through pull-down assays with the human DUB library, we identified OTUD6A as an Aurora-A-specific DUB. OTUD6A interacts with Aurora-A through OTU and kinase domains, respectively, and deubiquitinates Aurora-A. Notably, OTUD6A promotes the protein half-life of Aurora-A and activates Aurora-A by increasing phosphorylation at threonine 288 of Aurora-A. From qPCR screening, we identified and validated that the cancer gene <i>CKS2</i> encoding Cyclin-dependent kinases regulatory subunit 2 is the most upregulated cell cycle regulator when OTUD6A is overexpressed. The results suggest that OTUD6A may serve as a therapeutic target in human cancers.