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.
SUMOylation regulates the transcriptional activity of JunB in T lymphocytes
Garaude, J.; Farras, R.; Bossis, G.; Charni, S.; Piechaczyk, M.; Hipskind, R. A.; Villalba, M.
2008-05-01 / vol 180 / pages 5983-90
Humans; Jurkat Cells; CD4-Positive T-Lymphocytes/*immunology/metabolism; Chromatin/genetics/immunology/metabolism; Cytokines/biosynthesis/genetics/immunology; Lymphocyte Activation/genetics/*immunology; NFATC Transcription Factors/genetics/immunology/metabolism; Protein Processing, Post-Translational/genetics/*immunology; Proto-Oncogene Proteins c-jun/genetics/*immunology/metabolism; Response Elements/genetics/immunology; SUMO-1 Protein/genetics/*immunology/metabolism; Trans-Activation (Genetics)/genetics/immunology; Transcription Factor AP-1/genetics/immunology/metabolism; Transcription, Genetic/genetics/*immunology; Ubiquitin-Conjugating Enzymes/genetics/immunology/metabolism