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Single cell tuning of Myc expression by antigen receptor signal strength and interleukin‐2 in T lymphocytes
Author(s) -
Preston Gavin C,
Sinclair Linda V,
Kaskar Aneesa,
Hukelmann Jens L,
Navarro Maria N,
Ferrero Isabel,
MacDonald H Robson,
Cowling Victoria H,
Cantrell Doreen A
Publication year - 2015
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201490252
Subject(s) - biology , interleukin 2 , microbiology and biotechnology , antigen , receptor , t cell receptor , lymphocyte activation , immunology , cancer research , t cell , immune system , genetics
Myc controls the metabolic reprogramming that supports effector T cell differentiation. The expression of Myc is regulated by the T cell antigen receptor ( TCR ) and pro‐inflammatory cytokines such as interleukin‐2 ( IL ‐2). We now show that the TCR is a digital switch for Myc mRNA and protein expression that allows the strength of the antigen stimulus to determine the frequency of T cells that express Myc. IL ‐2 signalling strength also directs Myc expression but in an analogue process that fine‐tunes Myc quantity in individual cells via post‐transcriptional control of Myc protein. Fine‐tuning Myc matters and is possible as Myc protein has a very short half‐life in T cells due to its constant phosphorylation by glycogen synthase kinase 3 ( GSK 3) and subsequent proteasomal degradation. We show that Myc only accumulates in T cells exhibiting high levels of amino acid uptake allowing T cells to match Myc expression to biosynthetic demands. The combination of digital and analogue processes allows tight control of Myc expression at the population and single cell level during immune responses.