Open AccessTranslational Control by 4E-BP1/2 Suppressor Proteins Regulates Mitochondrial Biosynthesis and Function during CD8+ T Cell Proliferation
Author(s) -
Ioannis D. Dimitriou,
David Meiri,
Yulia Jitkova,
Alisha R. Elford,
Marianne Koritzinsky,
Aaron D. Schimmer,
Pamela S. Ohashi,
Nahum Sonenberg,
Robert Rottapel
Publication year - 2022
Publication title -
the journal of immunology
Language(s) - English
Resource type - Journals
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.2101090
Subject(s) - microbiology and biotechnology , effector , biology , pi3k/akt/mtor pathway , derepression , translation (biology) , cell growth , cytotoxic t cell , cd28 , t cell , biogenesis , protein biosynthesis , mtorc1 , mitochondrial biogenesis , mitochondrion , signal transduction , gene , gene expression , genetics , messenger rna , psychological repression , immune system , in vitro
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.
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