| Autor: |
Setou, Bin Chen, Md. Mahmudul Hasan, Hengsen Zhang, Qing Zhai, A. S. M. Waliullah, Yashuang Ping, Chi Zhang, Soho Oyama, Mst. Afsana Mimi, Yuna Tomochika, Yu Nagashima, Tomohiko Nakamura, Tomoaki Kahyo, Kenji Ogawa, Daita Kaneda, Minoru Yoshida, Mitsutoshi |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Biomedicines; Volume 11; Issue 6; Pages: 1685 |
| ISSN: |
2227-9059 |
| DOI: |
10.3390/biomedicines11061685 |
| Popis: |
Ubiquitin-like 3 (UBL3) acts as a post-translational modification (PTM) factor and regulates protein sorting into small extracellular vesicles (sEVs). sEVs have been reported as vectors for the pathology propagation of neurodegenerative diseases, such as α-synucleinopathies. Alpha-synuclein (α-syn) has been widely studied for its involvement in α-synucleinopathies. However, it is still unknown whether UBL3 interacts with α-syn, and is influenced by drugs or compounds. In this study, we investigated the interaction between UBL3 and α-syn, and any ensuing possible functional and pathological implications. We found that UBL3 can interact with α-syn by the Gaussiaprinceps based split luciferase complementation assay in cells and immunoprecipitation, while cysteine residues at its C-terminal, which are considered important as PTM factors for UBL3, were not essential for the interaction. The interaction was upregulated by 1-methyl-4-phenylpyridinium exposure. In drug screen results, the interaction was significantly downregulated by the treatment of osimertinib. These results suggest that UBL3 interacts with α-syn in cells and is significantly downregulated by epidermal growth factor receptor (EGFR) pathway inhibitor osimertinib. Therefore, the UBL3 pathway may be a new therapeutic target for α-synucleinopathies in the future. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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