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Here, we performed a whole genome CRISPR-Cas9 knockout screen under CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells pressure and identified the E3 ubiquitin ligase CUL5 as an essential factor required for escaping CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells killing in bladder cancer cells. We found that CUL5 knockout promoted the sensitivity of bladder cancer cells to CD8\n                    <jats:sup>+<\/jats:sup>\n                    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.\n                  <\/jats:p>","DOI":"10.1371\/journal.pbio.3003647","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T18:35:57Z","timestamp":1770662157000},"page":"e3003647","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["CUL5 E3 ubiquitin ligase regulates the evasion of bladder cancer cells to CD8+ T cell-mediated killing by inhibiting 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