Integrative proteomics reveals an increase in non-degradative ubiquitylation in activated CD4+ T cells

Nat Immunol. 2019 Jun;20(6):747-755. doi: 10.1038/s41590-019-0381-6. Epub 2019 May 6.

Abstract

Despite gathering evidence that ubiquitylation can direct non-degradative outcomes, most investigations of ubiquitylation in T cells have focused on degradation. Here, we integrated proteomic and transcriptomic datasets from primary mouse CD4+ T cells to establish a framework for predicting degradative or non-degradative outcomes of ubiquitylation. Di-glycine remnant profiling was used to reveal ubiquitylated proteins, which in combination with whole-cell proteomic and transcriptomic data allowed prediction of protein degradation. Analysis of ubiquitylated proteins identified by di-glycine remnant profiling indicated that activation of CD4+ T cells led to an increase in non-degradative ubiquitylation. This correlated with an increase in non-proteasome-targeted K29, K33 and K63 polyubiquitin chains. This study revealed over 1,200 proteins that were ubiquitylated in primary mouse CD4+ T cells and highlighted the relevance of non-proteasomally targeted ubiquitin chains in T cell signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Gene Expression Profiling
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology*
  • Mass Spectrometry
  • Mice
  • Polyubiquitin / metabolism
  • Proteome*
  • Proteomics* / methods
  • Receptors, Antigen, T-Cell / metabolism
  • Signal Transduction
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Transcriptome
  • Ubiquitination

Substances

  • Proteome
  • Receptors, Antigen, T-Cell
  • Polyubiquitin