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Originally published In Press as doi:10.1074/jbc.M007854200 on January 24, 2001

J. Biol. Chem., Vol. 276, Issue 17, 14350-14358, April 27, 2001
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Identification and Characterization of a Novel Nuclear Factor of Activated T-cells-1 Isoform Expressed in Mouse Brain*

Simon PlyteDagger §, Marianna BoncristianoDagger , Elena Fattori, Federico Galvagni||, Silvia Rossi Paccani**, M. Bernardetta MajoliniDagger Dagger , Salvatore Oliviero||, Gennaro Ciliberto, John L. Telford§§, and Cosima T. Baldari¶¶

From the Departments of Evolutionary Biology and || Molecular Biology, University of Siena, and the §§ Chiron Research Center, Via Fiorentina 1, 53100 Siena, Italy, and  IRBM, Via Pontina km 30.600, 00040 Pomezia, RM, Italy

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.

* This work was supported in part by the Italian Association for Cancer Research (AIRC), Telethon Grant E. 651, the Ministero per l'Università e la Ricerca Scientifica e Techologica (MURST), and the University of Siena (Piano di Ateneo per la Ricerca (PAR).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AF289078.

Dagger The first two authors contributed equally to this work.

§ Recipient of a long term European Molecular Biology Organization fellowship. Present address: Pharmacia and Upjohn SpA, Viale Pasteur 10, 20014 Nerviano Milan, Italy.

** Recipient of a fellowship from the University of Siena.

Dagger Dagger Recipient of an Italian Federation for Cancer Research (FIRC) fellowship.

¶¶ To whom correspondence should be addressed. Tel.: 39-0577-232-873; Fax: 39-0577-232-898; E-mail baldari@unisi.it.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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