title: SUMOylation regulates the transcriptional activity of JunB in T lymphocytes.
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.
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5535, 1919 route de Mende, Montpellier cedex 5, France. jgaraude@gmail.com
authors.forename: Johan
authors.initials: J
authors.lastname: Garaude
authors.forename: Rosa
authors.initials: R
authors.lastname: Farrás
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bossis
authors.forename: Seyma
authors.initials: S
authors.lastname: Charni
authors.forename: Marc
authors.initials: M
authors.lastname: Piechaczyk
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hipskind
authors.forename: Martin
authors.initials: M
authors.lastname: Villalba
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D050778:NFATC Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000235:genetics / Q000276:immunology*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020218:Response Elements / Q000235:genetics / Q000276:immunology; D025842:SUMO-1 Protein / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics / Q000276:immunology*; D015533:Transcriptional Activation / Q000235:genetics / Q000276:immunology; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D002843:Chromatin; D016207:Cytokines; D050778:NFATC Transcription Factors; D016755:Proto-Oncogene Proteins c-jun; D025842:SUMO-1 Protein; D018808:Transcription Factor AP-1; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9