Single cell tuning of Myc expression by antigen receptor signal strength and interleukin-2 in T lymphocytes.

Détails

ID Serval
serval:BIB_23E4F0ED2504
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Single cell tuning of Myc expression by antigen receptor signal strength and interleukin-2 in T lymphocytes.
Périodique
EMBO Journal
Auteur(s)
Preston G.C., Sinclair L.V., Kaskar A., Hukelmann J.L., Navarro M.N., Ferrero I., MacDonald H.R., Cowling V.H., Cantrell D.A.
ISSN
1460-2075 (Electronic)
ISSN-L
0261-4189
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
34
Numéro
15
Pages
2008-2024
Langue
anglais
Résumé
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 (GSK3) 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.
Mots-clé
cytokine signals, metabolism, Myc, T lymphocytes, TCR signals
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/08/2015 18:28
Dernière modification de la notice
08/05/2019 15:49
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