Abstract
The second messenger calcium plays an essential role in the T cell receptor-mediated signal transduction pathways leading to transcription of the interleukin-2 gene. A key mechanism of calcium signaling has been shown to be mediated by calcineurin and NFAT. We report herein that the transcription factor myocyte enhancer factor (MEF)-2 is another calcium signal transducer involved in the regulation of the interleukin (IL)-2 promoter. A MEF2-binding site was identified in proximity to the TATA box of the IL-2 promoter. This site was shown to be bound by MEF2 in both resting and activated T cells. Overexpression of MEF2 enhanced, while overexpression of a dominant negative form of MEF2 or the MEF2-specific transcriptional corepressors Cabin1 and histone deacetylase 4 inhibited, the T cell receptor-dependent activation of an IL-2 reporter gene. Down-regulation of MEF2 by RNA interference in primary human T cells led to the inhibition of endogenous IL-2 transcription. These results suggest that MEF2 is required for the transcriptional activation of IL-2 and likely other cytokine genes in response to calcium signaling and may serve as a novel target for development of immunosuppressants.
Original language | English (US) |
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Pages (from-to) | 14477-14480 |
Number of pages | 4 |
Journal | Journal of Biological Chemistry |
Volume | 279 |
Issue number | 15 |
DOIs | |
State | Published - Apr 9 2004 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology