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- W4313237717 abstract "Abstract Systematic identification of signaling pathways required for the fitness of cancer cells will facilitate the development of new cancer therapies. We used gene essentiality measurements in 1,086 cancer cell lines to identify selective coessentiality modules and found that a ubiquitin ligase complex composed of UBA6, BIRC6, KCMF1, and UBR4 is required for the survival of a subset of epithelial tumors that exhibit a high degree of aneuploidy. Suppressing BIRC6 in cell lines that are dependent on this complex led to a substantial reduction in cell fitness in vitro and potent tumor regression in vivo. Mechanistically, BIRC6 suppression resulted in selective activation of the integrated stress response (ISR) by stabilization of the heme-regulated inhibitor, a direct ubiquitination target of the UBA6/BIRC6/KCMF1/UBR4 complex. These observations uncover a novel ubiquitination cascade that regulates ISR and highlight the potential of ISR activation as a new therapeutic strategy. Significance: We describe the identification of a heretofore unrecognized ubiquitin ligase complex that prevents the aberrant activation of the ISR in a subset of cancer cells. This provides a novel insight on the regulation of ISR and exposes a therapeutic opportunity to selectively eliminate these cancer cells. See related commentary Leli and Koumenis, p. 535. This article is highlighted in the In This Issue feature, p. 517" @default.
- W4313237717 created "2023-01-06" @default.
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- W4313237717 date "2022-12-28" @default.
- W4313237717 modified "2023-10-05" @default.
- W4313237717 title "A Ubiquitination Cascade Regulating the Integrated Stress Response and Survival in Carcinomas" @default.
- W4313237717 cites W1840701820 @default.
- W4313237717 cites W1965440903 @default.
- W4313237717 cites W1965707365 @default.
- W4313237717 cites W1970090817 @default.
- W4313237717 cites W1971421925 @default.
- W4313237717 cites W1976290313 @default.
- W4313237717 cites W1976442562 @default.
- W4313237717 cites W1985665318 @default.
- W4313237717 cites W1986048086 @default.
- W4313237717 cites W1993501781 @default.
- W4313237717 cites W1999390452 @default.
- W4313237717 cites W2005504138 @default.
- W4313237717 cites W2010428875 @default.
- W4313237717 cites W2012166934 @default.
- W4313237717 cites W2016246269 @default.
- W4313237717 cites W2017289279 @default.
- W4313237717 cites W2019425923 @default.
- W4313237717 cites W2019762861 @default.
- W4313237717 cites W2023374667 @default.
- W4313237717 cites W2025483501 @default.
- W4313237717 cites W2026706790 @default.
- W4313237717 cites W2038291983 @default.
- W4313237717 cites W2040640278 @default.
- W4313237717 cites W2056654402 @default.
- W4313237717 cites W2073881294 @default.
- W4313237717 cites W2077813812 @default.
- W4313237717 cites W2077829361 @default.
- W4313237717 cites W2080788671 @default.
- W4313237717 cites W2081514938 @default.
- W4313237717 cites W2092269740 @default.
- W4313237717 cites W2099505694 @default.
- W4313237717 cites W2102049218 @default.
- W4313237717 cites W2114104545 @default.
- W4313237717 cites W2115603990 @default.
- W4313237717 cites W2120735622 @default.
- W4313237717 cites W2126859035 @default.
- W4313237717 cites W2128327076 @default.
- W4313237717 cites W2130410032 @default.
- W4313237717 cites W2135743049 @default.
- W4313237717 cites W2137526110 @default.
- W4313237717 cites W2144078529 @default.
- W4313237717 cites W2146512944 @default.
- W4313237717 cites W2152740213 @default.
- W4313237717 cites W2160644663 @default.
- W4313237717 cites W2162437451 @default.
- W4313237717 cites W2192080449 @default.
- W4313237717 cites W2199551899 @default.
- W4313237717 cites W2214074259 @default.
- W4313237717 cites W2237475663 @default.
- W4313237717 cites W2252568502 @default.
- W4313237717 cites W2257573908 @default.
- W4313237717 cites W2287840388 @default.
- W4313237717 cites W2400186996 @default.
- W4313237717 cites W2402118151 @default.
- W4313237717 cites W2467077495 @default.
- W4313237717 cites W2518855060 @default.
- W4313237717 cites W2518959324 @default.
- W4313237717 cites W2522417827 @default.
- W4313237717 cites W2583487304 @default.
- W4313237717 cites W2584033231 @default.
- W4313237717 cites W2735132087 @default.
- W4313237717 cites W2739511077 @default.
- W4313237717 cites W2741508285 @default.
- W4313237717 cites W2761629985 @default.
- W4313237717 cites W2787979900 @default.
- W4313237717 cites W2789268515 @default.
- W4313237717 cites W2795441313 @default.
- W4313237717 cites W2799333734 @default.
- W4313237717 cites W2803544880 @default.
- W4313237717 cites W2803828233 @default.