Tumor fitness coessentiality gene analysis that aims to expand the repertoire of druggable targets reveals a novel ubiquitin ligase complex, the BICR6 module. Along with the other complex members (UBA6, KCMF1, and UBR4), BIRC6 selectively contributes to the survival of a subset of epithelial tumors with a high degree of aneuploidy by ubiquitinating and suppressing HRI, a component of the integrated stress response adaptive pathway. See related article by Cervia et al., p. 766 (2).
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