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CUL5 E3 ubiquitin ligase regulates the evasion of bladder cancer cells to CD8+ T cell-mediated killing by inhibiting autophagy

GSE279149 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2026/01/29 Platform GPL29480
Summary
CD8+ T cells are capable of specifically targeting and eliminating malignant tumor cells, but tumor cells can develop resistance mechanisms to escape CD8+ T cell-mediated killing. Here, we performed a whole genome CRISPR-Cas9 knockout screen under CD8+ T cells pressure and identified the E3 ubiquitin ligase CUL5 as an essential factor required for escaping CD8+ T cells killing in bladder cancer cells. We found that CUL5 knockout promoted the sensitivity of bladder cancer cells to CD8+ T cell-mediated killing both in vivo and in vitro. Mechanistically, CUL5 loss reduced the ubiquitination of PTBP1, which regulated alternative splicing of RUBCN pre-mRNA and led to an increase in the levels of the RUBCN-S isoform, thereby preventing immune evasion of bladder cancer cells by inhibiting autophagy. Importantly, CUL5 knockout significantly enhanced the efficacy of anti-PD-1 immunotherapy in a xenograft model. Collectively, these findings reveal a novel mechanism of bladder cancer immune evasion, providing potential targets for cancer immunotherapy.
Published in
CUL5 E3 ubiquitin ligase regulates the evasion of bladder cancer cells to CD8+ T cell-mediated killing by inhibiting autophagy
Gao X, Yu Y, Sun J et al. · PLoS biology 2026 · PMID 41662369 · doi:10.1371/journal.pbio.3003647
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Also filed as BioProject PRJNA1170991 and SRA study SRP537527. Searching any of these in the dataset finder brings you back here.

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