Cited by 596PI3K/AKT/mTOR signaling in cancerT-cell and B-cell ImmunologyCancer, Hypoxia, and Metabolism

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PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8+ T cells

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Finlay, David K., Rosenzweig, Ella, Sinclair, Linda V., Feijoo-Carnero, Carmen, Hukelmann, Jens L., Rolf, Julia, Panteleyev, Andrey A., Okkenhaug, Klaus, Cantrell, Doreen A.·2012·Journal of Experimental Medicine

DOI 10.1084/jem.20112607PMC PMC3526360

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Abstract

mTORC1 (mammalian target of rapamycin complex 1) controls transcriptional programs that determine CD8+ cytolytic T cell (CTL) fate. In some cell systems, mTORC1 couples phosphatidylinositol-3 kinase (PI3K) and Akt to the control of glucose uptake and glycolysis. However, PI3K–Akt-independent mechanisms control glucose metabolism in CD8+ T cells, and the role of mTORC1 has not been explored. The present study now demonstrates that mTORC1 activity in CD8+ T cells is not dependent on PI3K or Akt but is critical to sustain glucose uptake and glycolysis in CD8+ T cells. We also show that PI3K- and Akt-independent pathways mediated by mTORC1 regulate the expression of HIF1 (hypoxia-inducible factor 1) transcription factor complex. This mTORC1–HIF1 pathway is required to sustain glucose metabolism and glycolysis in effector CTLs and strikingly functions to couple mTORC1 to a diverse transcriptional program that controls expression of glucose transporters, multiple rate-limiting glycolytic enzymes, cytolytic effector molecules, and essential chemokine and adhesion receptors that regulate T cell trafficking. These data reveal a fundamental mechanism linking nutrient and oxygen sensing to transcriptional control of CD8+ T cell differentiation.

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Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890
MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification
Cox, J., & Mann, M. (2008) · Nature Biotechnology · doi:10.1038/nbt.1511 · Cited by 14,855
Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkn923 · Cited by 14,108
Prolonged Rapamycin Treatment Inhibits mTORC2 Assembly and Akt/PKB
Sarbassov, D. D., Ali, S. M., Sengupta, S., Sheen, J.-H., Hsu, P. P., Bagley, A. F., Markhard, A. L., & Sabatini, D. M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.03.029 · Cited by 2,365
The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation
Wang, R., Dillon, C. P., Shi, L. Z., Milasta, S., Carter, R., Finkelstein, D., McCormick, L. L., Fitzgerald, P., Chi, H., Munger, J., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.09.021 · Cited by 2,140 · cited 4×
“In this respect, a previous study has implicated c-myc as a major regulator of glucose metabolism in T cells (Wang et al., 2011).”
BackgroundInfluential
HIF1α–dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells
Shi, L. Z., Wang, R., Huang, G., Vogel, P., Neale, G., Green, D. R., & Chi, H. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20110278 · Cited by 1,803
mTOR regulates memory CD8 T-cell differentiation
Araki, K., Turner, A. P., Shaffer, V. O., Gangappa, S., Keller, S. A., Bachmann, M. F., Larsen, C. P., & Ahmed, R. (2009) · Nature · doi:10.1038/nature08155 · Cited by 1,575
HIF-1: upstream and downstream of cancer metabolism
Semenza, G. L. (2009) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2009.10.009 · Cited by 1,431
The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2
Delgoffe, G. M., Pollizzi, K. N., Waickman, A. T., Heikamp, E., Meyers, D. J., Horton, M. R., Xiao, B., Worley, P. F., & Powell, J. D. (2011) · Nature Immunology · doi:10.1038/ni.2005 · Cited by 1,141
Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen
Pircher, H., Bürki, K., Lang, R., Hengartner, H., & Zinkernagel, R. M. (1989) · Nature · doi:10.1038/342559a0 · Cited by 1,019

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Authors: Finlay, D. K., Rosenzweig, E., Sinclair, L. V., Feijoo-Carnero, C., Hukelmann, J. L., Rolf, J., Panteleyev, A. A., Okkenhaug, K., & Cantrell, D. A.
Affiliations: Trinity College Dublin (IE)
University of Dundee (GB)
Division of Cell Signalling and Immunology, College of Life Sciences 3 ; and 4
Babraham Institute (GB)
Corresponding author: Finlay, David K.
Cantrell, Doreen A.
ORCID: Finlay, David K.
Sinclair, Linda V.
Hukelmann, Jens L.
Panteleyev, Andrey A.
Okkenhaug, Klaus
Cantrell, Doreen A.
Venue: Journal of Experimental Medicine
Publisher: Rockefeller University Press
Published: 2012-11-26
Volume: 209
Issue: 13
Pages: 2441-2453
ISSN: 0022-1007 (ISSN-L)
1540-9538
DOI: 10.1084/jem.20112607
PMC: PMC3526360
OpenAlex: W2164164239
Cited by: 596
References: 35
Citations by year: 2026: 29 · 2025: 33 · 2024: 32 · 2023: 43 · 2022: 46 · 2021: 59 · 2020: 47 · 2019: 56 · 2018: 45 · 2017: 43 · 2016: 49 · 2015: 46 · 2014: 36 · 2013: 29 · 2012: 2
FWCI: 14.52
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: The Journal of Experimental Medicine (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
Discovery Research Portal (University of Dundee) (acceptedVersion, other-oa)
Arrow@dit (Dublin Institute of Technology) (acceptedVersion)
Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion, cc-by-nc-sa)
Apollo (University of Cambridge) (submittedVersion, cc-by-nc-sa)
Apollo
Funders: University of Dundee
Wellcome Trust (097418/Z/11/Z, 095691, 065975, 097418)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords: mTORC1, CD8+ T cells, cytotoxic T lymphocytes, HIF-1, glucose metabolism, glycolysis, glucose uptake, T cell migration, T cell differentiation, nutrient sensing, oxygen sensing, glucose transporters, chemokine receptors, cell adhesion receptors
MeSH terms: Mechanistic Target of Rapamycin Complex 1, Animals, Cell Differentiation, Cell Movement, Gene Expression Regulation, Glucose, Glycolysis, Interleukin-2, Mice, Inbred C57BL, Mice, Mutant Strains, Mice, Transgenic, Proteins, Receptors, Antigen, T-Cell, Protein Serine-Threonine Kinases, CD8-Positive T-Lymphocytes, Chemokines, Receptors, Chemokine, Phosphatidylinositol 3-Kinases, Multiprotein Complexes, Proto-Oncogene Proteins c-akt, Mice, Aryl Hydrocarbon Receptor Nuclear Translocator, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit, TOR Serine-Threonine Kinases, 3-Phosphoinositide-Dependent Protein Kinases

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PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8+ T cells

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