Identification and Characterization of a Novel Nuclear Factor of Activated T-cells-1 Isoform Expressed in Mouse Brain

Simon Plyte, Marianna Boncristiano, Elena Fattori, Federico Galvagni, Silvia Rossi Paccani, M. Bernardetta Majolin, Salvatore Oliviero, Gennaro Ciliberto, John L. Telford, Cosima T. Baldari

Research output: Contribution to journalArticle

Abstract

The nuclear factor of activated T-cells (NFAT) family transcription factors play a key role in the control of cytokine gene expression in T-cells. Although initially identified in T-cells, recent data have unveiled unanticipated roles for NFATs in the development, proliferation, and differentiation of other tissues. Here we report the identification, cDNA cloning, and functional characterization of a new isoform of NFAT1 highly expressed in mouse brain. This isoform, which we named NFAT1-D, is identical to NFAT1 throughout the N-terminal regulatory domain and the portion of the Rel domain which includes the minimal region required for specific binding to DNA and interaction with AP-1. The homology stops sharply upstream of the 3′-boundary of the Rel homology domain and is followed by a short unique C-terminal region. NFAT1-D was expressed at high levels in all brain districts and was found as a constitutively active transcription complex. Transfection of a NFAT/luciferase reporter in the neuronal cell line PC12, which also expresses NFAT1-D, showed that these cells expressed a constitutive NFAT activity that was enhanced after nerve growth factor-induced differentiation but was resistant to the immunosuppressant cyclosporin A. NFAT1-D was, however, inducibly activated in a cyclosporin A-sensitive manner when expressed in T-cells, suggesting that the activity of NFAT proteins might be controlled by their specific cellular context.

Original languageEnglish
Pages (from-to)14350-14358
Number of pages9
JournalJournal of Biological Chemistry
Volume276
Issue number17
DOIs
Publication statusPublished - Apr 27 2001

ASJC Scopus subject areas

  • Biochemistry

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    Plyte, S., Boncristiano, M., Fattori, E., Galvagni, F., Paccani, S. R., Majolin, M. B., Oliviero, S., Ciliberto, G., Telford, J. L., & Baldari, C. T. (2001). Identification and Characterization of a Novel Nuclear Factor of Activated T-cells-1 Isoform Expressed in Mouse Brain. Journal of Biological Chemistry, 276(17), 14350-14358. https://doi.org/10.1074/jbc.M007854200