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 Enzyme UBC9
-
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