title: The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation.
abstract: To fulfill the bioenergetic and biosynthetic demand of proliferation, T cells reprogram their metabolic pathways from fatty acid β-oxidation and pyruvate oxidation via the TCA cycle to the glycolytic, pentose-phosphate, and glutaminolytic pathways. Two of the top-ranked candidate transcription factors potentially responsible for the activation-induced T cell metabolic transcriptome, HIF1α and Myc, were induced upon T cell activation, but only the acute deletion of Myc markedly inhibited activation-induced glycolysis and glutaminolysis in T cells. Glutamine deprivation compromised activation-induced T cell growth and proliferation, and this was partially replaced by nucleotides and polyamines, implicating glutamine as an important source for biosynthetic precursors in active T cells. Metabolic tracer analysis revealed a Myc-dependent metabolic pathway linking glutaminolysis to the biosynthesis of polyamines. Therefore, a Myc-dependent global metabolic transcriptome drives metabolic reprogramming in activated, primary T lymphocytes. This may represent a general mechanism for metabolic reprogramming under patho-physiological conditions.
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Ruoning
authors.initials: R
authors.lastname: Wang
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Dillon
authors.forename: Lewis Zhichang
authors.initials: LZ
authors.lastname: Shi
authors.forename: Sandra
authors.initials: S
authors.lastname: Milasta
authors.forename: Robert
authors.initials: R
authors.lastname: Carter
authors.forename: David
authors.initials: D
authors.lastname: Finkelstein
authors.forename: Laura L
authors.initials: LL
authors.lastname: McCormick
authors.forename: Patrick
authors.initials: P
authors.lastname: Fitzgerald
authors.forename: Hongbo
authors.initials: H
authors.lastname: Chi
authors.forename: Joshua
authors.initials: J
authors.lastname: Munger
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Green
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D053858:Metabolic Networks and Pathways / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009952:Ornithine / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D059467:Transcriptome
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011073:Polyamines; D016271:Proto-Oncogene Proteins c-myc; D005973:Glutamine; D009952:Ornithine; D058570:TOR Serine-Threonine Kinases; D005947:Glucose