Stefanie Schmidt, David Gay, Friedrich Wilhelm Uthe, Sarah Denk, Madelon Paauwe, Niels Matthes, Markus Elmar Diefenbacher, Sheila Bryson, Fiona Clare Warrander, Florian Erhard, Carsten Patrick Ade, Apoorva Baluapuri, Susanne Walz, Rene Jackstadt, Catriona Ford, Georgios Vlachogiannis, Nicola Valeri, Christoph Otto, Christina Schülein-Völk, Katja Maurus, Werner Schmitz, John Raymond Philip Knight, Elmar Wolf, Douglas Strathdee, Almut Schulze, Christoph-Thomas Germer, Andreas Rosenwald, Owen James Sansom, Martin Eilers, Armin Wiegering
Tumours depend on altered rates of protein synthesis for growth and survival, which suggests that mechanisms controlling mRNA translation may be exploitable for therapy. Here, we show that loss of APC, which occurs almost universally in colorectal tumours, strongly enhances the dependence on the translation initiation factor eIF2B5. Depletion of eIF2B5 induces an integrated stress response and enhances translation of MYC via an internal ribosomal entry site. This perturbs cellular amino acid and nucleotide pools, strains energy resources and causes MYC-dependent apoptosis...
November 4, 2019: Nature Cell Biology