| First Author | He C | Year | 2024 |
| Journal | Mol Cell | Volume | 84 |
| Issue | 6 | Pages | 1120-1138.e8 |
| PubMed ID | 38377992 | Mgi Jnum | J:347152 |
| Mgi Id | MGI:7616062 | Doi | 10.1016/j.molcel.2024.01.024 |
| Citation | He C, et al. (2024) UFL1 ablation in T cells suppresses PD-1 UFMylation to enhance anti-tumor immunity. Mol Cell 84(6):1120-1138.e8 |
| abstractText | UFMylation is an emerging ubiquitin-like post-translational modification that regulates various biological processes. Dysregulation of the UFMylation pathway leads to human diseases, including cancers. However, the physiological role of UFMylation in T cells remains unclear. Here, we report that mice with conditional knockout (cKO) Ufl1, a UFMylation E3 ligase, in T cells exhibit effective tumor control. Single-cell RNA sequencing analysis shows that tumor-infiltrating cytotoxic CD8(+) T cells are increased in Ufl1 cKO mice. Mechanistically, UFL1 promotes PD-1 UFMylation to antagonize PD-1 ubiquitination and degradation. Furthermore, AMPK phosphorylates UFL1 at Thr536, disrupting PD-1 UFMylation to trigger its degradation. Of note, UFL1 ablation in T cells reduces PD-1 UFMylation, subsequently destabilizing PD-1 and enhancing CD8(+) T cell activation. Thus, Ufl1 cKO mice bearing tumors have a better response to anti-CTLA-4 immunotherapy. Collectively, our findings uncover a crucial role of UFMylation in T cells and highlight UFL1 as a potential target for cancer treatment. |
