Interferon regulatory factor 2 binding protein 2 is a new NFAT1 partner and represses its transcriptional activity.
The nuclear factor of activated T cells (NFAT) family of transcription factors is expressed in a wide range of cell types and regulates genes involved in cell cycle, differentiation, and apoptosis. NFAT proteins share two well-conserved regions, the regulatory domain and the DNA binding domain. The N- and C-terminal ends ... are transactivation sites and show less sequence similarity, whereas their molecular functions remain poorly understood. Here, we identified a transcriptional repressor, interferon regulatory factor 2 binding protein 2 (IRF-2BP2), which specifically interacts with the C-terminal domain of NFAT1 among the NFAT family members. IRF-2BP2 was described as a corepressor by inhibiting both enhancer-activated and basal transcription. Gene reporter assays demonstrated that IRF-2BP2 represses the NFAT1-dependent transactivation of NFAT-responsive promoters. The ectopic expression of IRF-2BP2 in CD4 T cells resulted in decreased interleukin-2 (IL-2) and IL-4 production, supporting a repressive function of IRF-2BP2 for NFAT target genes. Furthermore, NFAT1 and IRF-2BP2 colocalized in the nucleus in activated cells, and the mutation of a newly identified nuclear localization signal in the IRF-2BP2 rendered it cytoplasmic, abolishing its repressive effect on NFAT1 activity. Collectively, our data demonstrate that IRF-2BP2 is a negative regulator of the NFAT1 transcription factor and suggest that NFAT1 repression occurs at the transcriptional level.
Mesh Terms:
Amino Acid Sequence, Animals, CD4-Positive T-Lymphocytes, Carrier Proteins, Cells, Cultured, Gene Expression Regulation, HEK293 Cells, Humans, Interferon Regulatory Factor-2, Mice, Molecular Sequence Data, NFATC Transcription Factors, Nuclear Localization Signals, Nuclear Proteins, Protein Binding, Sequence Alignment, Transcription, Genetic, Two-Hybrid System Techniques
Amino Acid Sequence, Animals, CD4-Positive T-Lymphocytes, Carrier Proteins, Cells, Cultured, Gene Expression Regulation, HEK293 Cells, Humans, Interferon Regulatory Factor-2, Mice, Molecular Sequence Data, NFATC Transcription Factors, Nuclear Localization Signals, Nuclear Proteins, Protein Binding, Sequence Alignment, Transcription, Genetic, Two-Hybrid System Techniques
Mol. Cell. Biol.
Date: Jul. 01, 2011
PubMed ID: 21576369
View in: Pubmed Google Scholar
Download Curated Data For This Publication
146955
Switch View:
- Interactions 3