Quantitative analysis of how Myc controls T cell proteomes and metabolic pathways during T cell activation

Julia Marchingo, Linda Sinclair (Lead / Corresponding author), Andy Howden, Doreen Cantrell (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)
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Abstract

T cell expansion and differentiation are critically dependent on the transcription factor c-Myc (Myc). Herein we use quantitative mass-spectrometry to reveal how Myc controls antigen receptor driven cell growth and proteome restructuring in murine T cells. Analysis of copy numbers per cell of >7000 proteins provides new understanding of the selective role of Myc in controlling the protein machinery that govern T cell fate. The data identify both Myc dependent and independent metabolic processes in immune activated T cells. We uncover that a primary function of Myc is to control expression of multiple amino acid transporters and that loss of a single Myc-controlled amino acid transporter effectively phenocopies the impact of Myc deletion. This study provides a comprehensive map of how Myc selectively shapes T cell phenotypes, revealing that Myc induction of amino acid transport is pivotal for subsequent bioenergetic and biosynthetic programs and licences T cell receptor driven proteome reprogramming.
Original languageEnglish
Article numbere53725
Pages (from-to)1-23
Number of pages23
JournaleLife
Volume9
Early online date5 Feb 2020
DOIs
Publication statusPublished - 4 Mar 2020

Keywords

  • Myc
  • T cell activation
  • T lymphocyte
  • amino acid transport
  • immunology
  • inflammation
  • mouse
  • proteomics

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