OTUD6A Is an Aurora Kinase A-Specific Deubiquitinase.
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 CKS2 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.
Mesh Terms:
Aurora Kinase A, CDC2-CDC28 Kinases, Cell Cycle Proteins, Deubiquitinating Enzymes, Gene Expression, HEK293 Cells, Half-Life, Humans, Open Reading Frames, Phosphorylation, Protein Stability, Real-Time Polymerase Chain Reaction, Transcription, Genetic, Transfection
Aurora Kinase A, CDC2-CDC28 Kinases, Cell Cycle Proteins, Deubiquitinating Enzymes, Gene Expression, HEK293 Cells, Half-Life, Humans, Open Reading Frames, Phosphorylation, Protein Stability, Real-Time Polymerase Chain Reaction, Transcription, Genetic, Transfection
Int J Mol Sci
Date: Feb. 16, 2021
PubMed ID: 33669244
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