FBXL20‐mediated ubiquitination triggers the proteasomal degradation of 4‐1BB
| العنوان: | FBXL20‐mediated ubiquitination triggers the proteasomal degradation of 4‐1BB |
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| المؤلفون: | Ruoxuan Sun, Seung‐Oe Lim |
| المصدر: | The FEBS Journal. 289:4549-4563 |
| بيانات النشر: | Wiley, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Transcriptional Activation, Tumor Necrosis Factor Receptor Superfamily, Member 9, F-Box Proteins, Neoplasms, T-Lymphocytes, Ubiquitination, Humans, Cell Biology, Molecular Biology, Biochemistry |
| الوصف: | 4-1BB [tumor necrosis factor receptor superfamily (TNFRSF9), CD137) is a critical immune stimulator that sustains T cell activity and antitumor immune response. The strategy to eliminate cancers by agonistically targeting 4-1BB is under clinical investigation. As a protein expressed in an inducible manner, 4-1BB is under tight control on both transcription and translation levels to maintain its homeostasis. So far, the mechanisms underlying the transcriptional activation of 4-1BB have been well-interpreted; however, it remains inexplicit how 4-1BB is regulated on the protein level. In this study, we presented experimental evidence supporting that 4-1BB, especially the heavily N-glycosylated (mature) form, is polyubiquitinated and subjected to the ubiquitin-proteasomal system for degradation. By performing proximity-dependent biotin identification screening coupled with biochemical assays, we identified that F-box/LRR-repeat protein 20 acts as the E3 ligase that promotes the polyubiquitination of 4-1BB at the intracellular domain. Our data provided mechanistic insight into 4-1BB regulation on the protein level by unmasking, for the first time, a posttranslational mechanism governing 4-1BB abundance in cells. The findings of this study could potentially guide the development of 4-1BB-targeted therapy for cancers as well as other immune disorders. |
| تدمد: | 1742-4658 1742-464X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9b777c52fdf0f6b141c25a012da5d281 https://doi.org/10.1111/febs.16383 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....9b777c52fdf0f6b141c25a012da5d281 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17424658 1742464X |
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