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Requirement for transcription factor NFAT in interleukin-2 expression
C W Chow1, M Rincón, R J Davis
1Howard Hughes Medical Institute and Program in Molecular Medicine, Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Molecular and Cellular Biology
|February 18, 1999
Summary
Nuclear Factor of Activated T cells (NFAT) is crucial for regulating Interleukin-2 (IL-2) gene expression. A novel dominant-negative NFAT mutant confirmed NFAT
Area of Science:
- Immunology
- Molecular Biology
- Transcription Factors
Background:
- Nuclear Factor of Activated T cells (NFAT) is linked to Interleukin-2 (IL-2) expression.
- NFAT binding sites exist in the IL-2 promoter, and Cyclosporin A inhibits both NFAT and IL-2.
- Previous gene disruption studies in mice yielded unclear results regarding NFAT's role in IL-2 regulation.
Purpose of the Study:
- To clarify the role of NFAT in regulating IL-2 gene expression.
- To develop a tool to selectively inhibit NFAT-mediated gene expression.
Main Methods:
- Construction of a dominant-negative NFAT mutant (dnNFAT).
- Assessing dnNFAT's effect on IL-2 promoter activity and IL-2 protein expression in cultured T cells.
- Evaluating dnNFAT's impact on IL-2 gene expression in transgenic mice.
Main Results:
- The dnNFAT mutant effectively inhibited NFAT-mediated gene expression by blocking NFAT nuclear translocation.
- Expression of dnNFAT in T cells led to reduced IL-2 promoter activity and IL-2 protein levels.
- Transgenic mice expressing dnNFAT exhibited decreased IL-2 gene expression.
Conclusions:
- NFAT is a critical component in the signaling pathway regulating IL-2 expression.
- The study validates the use of dnNFAT as a tool to study NFAT function.
- This research clarifies the previously ambiguous role of NFAT in IL-2 regulation.