Regulation of Human mRNA Transcription by NFAT and AP-1 Proteins:

The mammalian immune system represents a unique model for studying the importance of transcriptional regulation in governing cell growth and differentiation. Interleukin-2 is a cytokine that acts as an autocrine growth factor promoting the proliferation and development of T cells during the immune response to bacterial and viral infection, as well as tumorigenesis. The IL-2 promoter is relatively compact for mammalian genes, since proper regulation of IL-2 transcription requires only 340 bp of DNA surrounding the transcription start site. We have investigated the roles of both cis-regulatory elements and trans-regulatory factors (e.g., NFAT, AP1) in transcription at the IL-2 promoter using in vitro transcription experiments and assays in T cells. We have found that NFAT1 and cJun homodimers have a unique ability to interact with one another and that this interaction is critical for the synergistic activation of IL-2 transcription. We are now studying the role of these transcription factors in mediating synergy at other promoters and in other biological systems.

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Walters, R.D., Drullinger, L.F., Kugel, J.F., Goodrich, J.A. (2013). NFATc2 recruits cJun homodimers to an NFAT site to synergistically activate interleukin-2 transcription. Mol Immunol. In press.

Nguyen, T.N., Kim, L.J., Walters, R.D., Drullinger, L.F., Lively T.N., Kugel, J.F., and Goodrich, J.A. (2010) The C-terminal region of human NFATc2 binds cJun to synergistically activate interleukin-2 transcription. Mol Immunol. 47(14):2314-22

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