Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 2008-2024 |
| Number of pages | 17 |
| Journal | EMBO Journal |
| Volume | 34 |
| Issue number | 15 |
| DOIs | |
| Publication status | Published - 4 Aug 2015 |
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Keywords
- Cytokine signals
- Metabolism
- Myc
- T lymphocytes
- TCR signals
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Single cell tuning of Myc expression by antigen receptor signal strength and interleukin-2 in T lymphocytes. / Preston, Gavin C.; Sinclair, Linda V.; Kaskar, Aneesa; Hukelmann, Jens L.; Navarro, Maria; Ferrero, Isabel; MacDonald, H. Robson; Cowling, Victoria H.; Cantrell, Doreen A. (Lead / Corresponding author).
In: EMBO Journal, Vol. 34, No. 15, 04.08.2015, p. 2008-2024.Research output: Contribution to journal › Article
TY - JOUR
T1 - Single cell tuning of Myc expression by antigen receptor signal strength and interleukin-2 in T lymphocytes
AU - Preston, Gavin C.
AU - Sinclair, Linda V.
AU - Kaskar, Aneesa
AU - Hukelmann, Jens L.
AU - Navarro, Maria
AU - Ferrero, Isabel
AU - MacDonald, H. Robson
AU - Cowling, Victoria H.
AU - Cantrell, Doreen A.
PY - 2015/8/4
Y1 - 2015/8/4
N2 - 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.
AB - 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.
KW - Cytokine signals
KW - Metabolism
KW - Myc
KW - T lymphocytes
KW - TCR signals
UR - http://www.scopus.com/inward/record.url?scp=84938662913&partnerID=8YFLogxK
U2 - 10.15252/embj.201490252
DO - 10.15252/embj.201490252
M3 - Article
C2 - 26136212
AN - SCOPUS:84938662913
VL - 34
SP - 2008
EP - 2024
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 15
ER -