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

• Main Authors: Julia M Marchingo, Linda V Sinclair, Andrew JM Howden, Doreen A Cantrell
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2020-02-01
• Series: eLife
• Subjects: T lymphocyte; T cell activation; proteomics; Myc; amino acid transport
• Online Access: https://elifesciences.org/articles/53725

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.