SUMOylation regulates the transcriptional activity of JunB in T lymphocytes

J Immunol. 2008 May 1;180(9):5983-90. doi: 10.4049/jimmunol.180.9.5983.

Abstract

The AP-1 family member JunB is a critical regulator of T cell function. JunB is a transcriptional activator of various cytokine genes, such as IL-2, IL-4, and IL-10; however, the post-translational modifications that regulate JunB activity in T cells are poorly characterized. We show here that JunB is conjugated with small ubiquitin-like modifier (SUMO) on lysine 237 in resting and activated primary T cells and T cell lines. Sumoylated JunB associated with the chromatin-containing insoluble fraction of cells, whereas nonsumoylated JunB was also in the soluble fraction. Blocking JunB sumoylation by mutation or use of a dominant-negative form of the SUMO-E2 Ubc-9 diminished its ability to transactivate IL-2 and IL-4 reporter genes. In contrast, nonsumoylable JunB mutants showed unimpaired activity with reporter genes controlled by either synthetic 12-O-tetradecanoylphorbol-13-acetate response elements or NF-AT/AP-1 and CD28RE sites derived from the IL-2 promoter. Ectopic expression of JunB in activated human primary CD4(+) T cells induced activation of the endogenous IL-2 promoter, whereas the nonsumoylable JunB mutant did not. Thus, our work demonstrates that sumoylation of JunB regulates its ability to induce cytokine gene transcription and likely plays a critical role in T cell activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Chromatin / genetics
  • Chromatin / immunology
  • Chromatin / metabolism
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Cytokines / immunology
  • Humans
  • Jurkat Cells
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology*
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / immunology
  • NFATC Transcription Factors / metabolism
  • Protein Processing, Post-Translational / genetics
  • Protein Processing, Post-Translational / immunology*
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-jun / immunology*
  • Proto-Oncogene Proteins c-jun / metabolism
  • Response Elements / genetics
  • Response Elements / immunology
  • SUMO-1 Protein / genetics
  • SUMO-1 Protein / immunology*
  • SUMO-1 Protein / metabolism
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / immunology
  • Transcription Factor AP-1 / metabolism
  • Transcription, Genetic / genetics
  • Transcription, Genetic / immunology*
  • Transcriptional Activation / genetics
  • Transcriptional Activation / immunology
  • Ubiquitin-Conjugating Enzymes / genetics
  • Ubiquitin-Conjugating Enzymes / immunology
  • Ubiquitin-Conjugating Enzymes / metabolism

Substances

  • Chromatin
  • Cytokines
  • NFATC Transcription Factors
  • Proto-Oncogene Proteins c-jun
  • SUMO-1 Protein
  • Transcription Factor AP-1
  • Ubiquitin-Conjugating Enzymes
  • ubiquitin-conjugating enzyme UBC9