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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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BAP1 controls mesenchymal stem cell migration by inhibiting the ERK signaling pathway

  • Seobin Kim (Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Eun-Woo Lee (Metabolic Disease Research Center, KRIBB) ;
  • Doo-Byoung Oh (Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Jinho Seo (Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
  • Received : 2023.09.14
  • Accepted : 2023.11.09
  • Published : 2024.05.31
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Abstract

Due to their stem-like characteristics and immunosuppressive properties, Mesenchymal stem cells (MSCs) offer remarkable potential in regenerative medicine. 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.

Keywords

Acknowledgement

This work was supported by grants from the National Research Foundation of Korea [NRF-2020R1C1C1006833, NRF-2022 R1A2C1011353, and CRC22011-300] and the Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program [KGM5322321].

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