1. Translational Control by 4E-BP1/2 Suppressor Proteins Regulates Mitochondrial Biosynthesis and Function during CD8 + T Cell Proliferation.
- Author
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Dimitriou ID, Meiri D, Jitkova Y, Elford AR, Koritzinsky M, Schimmer AD, Ohashi PS, Sonenberg N, and Rottapel R
- Subjects
- Animals, CD8-Positive T-Lymphocytes metabolism, Cell Cycle Proteins metabolism, Cell Proliferation, Mammals genetics, Mice, Organelle Biogenesis, Phosphatidylinositol 3-Kinases metabolism, Phosphorylation, Protein Biosynthesis, Eukaryotic Initiation Factors genetics, Eukaryotic Initiation Factors metabolism, Phosphoproteins metabolism
- Abstract
CD8
+ T cell proliferation and differentiation into effector and memory states are high-energy processes associated with changes in cellular metabolism. CD28-mediated costimulation of T cells activates the PI3K/AKT/mammalian target of rapamycin signaling pathway and induces eukaryotic translation initiation factor 4E-dependent translation through the derepression by 4E-BP1 and 4E-BP2. In this study, we demonstrate that 4E-BP1/2 proteins are required for optimum proliferation of mouse CD8+ T cells and the development of an antiviral effector function. We show that translation of genes encoding mitochondrial biogenesis is impaired in T cells derived from 4E-BP1/2-deficient mice. Our findings demonstrate an unanticipated role for 4E-BPs in regulating a metabolic program that is required for cell growth and biosynthesis during the early stages of CD8+ T cell expansion., (Copyright © 2022 by The American Association of Immunologists, Inc.)- Published
- 2022
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