Dr. Lee, Yu-Ru 's publons link picture



  • Cancer Genetics
  • Cancer Signaling, Post-translational Modifications, Non-coding RNAs
  • Cancer Biology, Targeted/Immunotherapy

Education and Positions:
    • Ph.D., Institute of Molecular Medicine, National Taiwan University College of Medicine
    • Instructor in BIDMC, Harvard Medical School
    • Post-doc in BIDMC, Harvard Medical School

Highlight Detail

UFL1 ablation in T cells suppresses PD-1 UFMylation to enhance anti-tumor immunity

Dr. Lee, Yu-Ru
Molecular Cell, Feb 19, 2024

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.