التفاصيل البيبلوغرافية
| العنوان: |
Overexpression of UBA5 in Cells Mimics the Phenotype of Cells Lacking UBA5 |
| المؤلفون: |
Sujata Kumari, Sayanika Banerjee, Manoj Kumar, Arata Hayashi, Balakrishnan Solaimuthu, Einav Cohen-Kfir, Yoav D. Shaul, Alexander Rouvinski, Reuven Wiener |
| المصدر: |
International Journal of Molecular Sciences; Volume 23; Issue 13; Pages: 7445 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2022 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
ufmylation, UBA5, UFC1, E1-activating enzymes, E2-conjugating enzymes, ubiquitin-like protein, UFM1 |
| جغرافية الموضوع: |
agris |
| الوصف: |
Ufmylation is a posttranslational modification in which the modifier UFM1 is attached to target proteins. This conjugation requires the concerted work of three enzymes named UBA5, UFC1, and UFL1. Initially, UBA5 activates UFM1 in a process that ends with UFM1 attached to UBA5’s active site Cys. Then, in a trans-thiolation reaction, UFM1 is transferred from UBA5 to UFC1, forming a thioester bond with the latter. Finally, with the help of UFL1, UFM1 is transferred to the final destination—a lysine residue on a target protein. Therefore, not surprisingly, deletion of one of these enzymes abrogates the conjugation process. However, how overexpression of these enzymes affects this process is not yet clear. Here we found, unexpectedly, that overexpression of UBA5, but not UFC1, damages the ability of cells to migrate, in a similar way to cells lacking UBA5 or UFC1. At the mechanistic level, we found that overexpression of UBA5 reverses the trans-thiolation reaction, thereby leading to a back transfer of UFM1 from UFC1 to UBA5. This, as seen in cells lacking UBA5, reduces the level of charged UFC1 and therefore harms the conjugation process. In contrast, co-expression of UBA5 with UFM1 abolishes this effect, suggesting that the reverse transfer of UFM1 from UFC1 to UBA5 depends on the level of free UFM1. Overall, our results propose that the cellular expression level of the UFM1 conjugation enzymes has to be tightly regulated to ensure the proper directionality of UFM1 transfer. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| Relation: |
Biochemistry; https://dx.doi.org/10.3390/ijms23137445 |
| DOI: |
10.3390/ijms23137445 |
| الاتاحة: |
https://doi.org/10.3390/ijms23137445 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: |
edsbas.402E4950 |
| قاعدة البيانات: |
BASE |