| BAP1 controls mesenchymal stem cell migration by inhibiting the ERK signaling pathway |
| Seobin Kim1,2 (Graduate student), Eun-Woo Lee3,4 (Senior Researcher), Doo-Byoung Oh1,2,# (Principal Investigator), Jinho Seo1,2,*,# (Senior Researcher) |
1Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB),
2Biosystems and Bioengineering, University of Science and Technology (UST),
3Metabolic Disease Research Center, KRIBB,
4Functional Genomics, UST |
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Abstract
Mesenchymal stem cells (MSCs) have remarkable potential in regenerative medicine owing to their stem-like characteristics and immunosuppressive properties. Much effort has been devoted to enhancing the efficacy of MSC therapy by enhancing MSC migration. In this study, we identified deubiquitinase BRCA1-associated protein 1 (BAP1) as an inhibitor of MSC migration. Using deubiquitinase siRNA library screening based on an in vitro wound healing assay, we found that silencing BAP1 significantly augmented MSC migration. Conversely, BAP1 overexpression reduced the migration and invasion capabilities of MSCs. BAP1 depletion in MSCs upregulates ERK phosphorylation, thereby increasing the expression of the migration factor osteopontin. Further examination revealed that BAP1 interacts with phosphorylated ERK1/2, deubiquitinating their ubiquitins, and thus attenuating the ERK signaling pathway. Overall, our study highlights the critical role of BAP1 in regulating MSC migration through its deubiquitinase activity and suggests a novel approach to improve the therapeutic potential of MSCs in regenerative medicine.
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| Abstract, Accepted Manuscript [Submitted on September 14, 2023, Accepted on November 9, 2023] |
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