| Autor: |
Tal Levy, Kai Voeltzke, Laura Hauffe, Khawla Alasad, Marteinn Snaebjörnsson, Ran Marciano, Katerina Scharov, Mélanie Planque, Kim Vriens, Stefan Christen, Cornelius M Funk, Christina Hassiepen, Alisa Kahler, Beate Heider, Daniel Picard, Jonathan KM Lim, Zuelal Bas, Katja Bendrin, Andres Vargas-Toscano, Ulf Kahlert, Marc Remke, Moshe Elkabets, Thomas GP Grünewald, Andreas S. Reichert, Sarah-Maria Fendt, Almut Schulze, Guido Reifenberger, Barak Rotblat, Gabriel Leprivier |
| Rok vydání: |
2022 |
| Popis: |
SUMMARYEnergetic stress compels cells to evolve adaptive mechanisms to maintain homeostasis. Here, we report that the negative regulators of mRNA translation initiation eukaryotic initiation factor 4E binding proteins 1/2 (4EBP1/2) are essential to promote the survival of mammalian cells and budding yeast under glucose starvation. Functionally, 4EBP1/2 inhibit fatty acid synthesis upon energetic stress via repression of Acetyl-CoA Carboxylase Alpha (ACACA) mRNA translation, sparing NADPH, to maintain intracellular redox balance. This has important relevance in cancers, as we uncovered that oncogene-transformed cells and glioma cells exploit the 4EBP1/2 regulation of ACACA expression and redox balance to combat energetic stress, thereby supporting transformation and tumorigenicity in vitro and in vivo. Clinically, high EIF4EBP1 (encoding 4EBP1) expression is associated with poor outcomes in several cancer types, including glioma. Our data reveal that 4EBP1/2 are conserved mediators of the survival response to energetic stress which are exploited by cancer cells for metabolic adaptation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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