Journal ArticleDOI
The T-cell transcription factor NFATp is a substrate for calcineurin and interacts with Fos and Jun.
Jugnu Jain,Patricia G. McCaffrey,Z. Miner,Z. Miner,Tom K. Kerppola,John Lambert,Gregory L. Verdine,Tom Curran,Anjana Rao +8 more
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TLDR
The interaction between the lymphoid-specific factor NFATp and the ubiquitous transcription factors Fos and Jun provides a novel mechanism for combinatorial regulation of interleukin-2 gene transcription, which integrates the calcium-dependent and the protein-kinase C-dependent pathways of T-cell activation.Abstract:
TRANSCRIPTION of lymphokine genes in activated T cells is inhibited by the immunosuppressive agents cyclosporin A and FK506, which act by blocking the phosphatase activity of calcineurin1–3. NFAT, a DNA-binding protein required for interleukin-2 gene transcription, is a potential target for calcineurin, cyclosporin A and FK5064–11. NFAT contains a subunit (NFATp) which is present in unstimulated T cells and which forms a complex with Fos and Jun proteins in the nucleus of activated T cells9,11. Here we report that NFATp is a DNA-binding phosphoprotein of relative molecular mass ∼ 120,000 and is a substrate for calcineurin in vitro. Purified NFATp forms DNA–protein complexes with recombinant Jun homodimers or Jun–Fos heterodimers; the DNA-binding domains of Fos and Jun are essential for the formation of the NFATp–Fos–Jun–DNA complex. The interaction between the lymphoid-specific factor NFATp and the ubiquitous transcription factors Fos and Jun provides a novel mechanism for combinatorial regulation of interleukin-2 gene transcription, which integrates the calcium-dependent and the protein-kinase C-dependent pathways of T-cell activation.read more
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Journal ArticleDOI
TRANSCRIPTION FACTORS OF THE NFAT FAMILY:Regulation and Function
TL;DR: Recent data on the diversity of the NFAT family of transcription factors, the regulation of NFAT proteins within cells, and the cooperation ofNFAT proteins with other transcription factors to regulate the expression of inducible genes are discussed.
Journal ArticleDOI
Signal transduction by lymphocyte antigen receptors
Arthur Weiss,Dan R. Littman +1 more
TL;DR: Insight gained from studies of the signaling pathways downstream of TCR and BCR stimulation is likely to contribute significantly to future understanding of mechanisms responsible for lymphocyte differentiation and for the discrimination of self from nonself in developing and mature cells.
Journal ArticleDOI
Transcriptional regulation by calcium, calcineurin, and NFAT
TL;DR: The NFAT family of transcription factors encompasses five proteins evolutionarily related to the Rel/NF B family, and it is clear that NFAT activates transcription of a large number of genes during an effective immune response.
Journal ArticleDOI
The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling.
Carol A. Grimes,Richard S. Jope +1 more
TL;DR: GSK3beta has a central role regulating neuronal plasticity, gene expression, and cell survival, and may be a key component of certain psychiatric and neurodegenerative diseases.
Journal ArticleDOI
Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins
T. Herdegen,J.D. Leah +1 more
TL;DR: This article reviews findings up to the end of 1997 about the inducible transcription factors c-Jun, JunB, JunD, c-Fos, FosB, Fra,1, Fra-2, Krox-20 (Egr-2) and Krox -24 (NGFI-A, Egr-1, Zif268) as they pertain to gene expression in the mammalian nervous system and describes their expression and possible roles in glial cells.
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Journal ArticleDOI
The mechanism of action of cyclosporin A and FK506
TL;DR: Recent findings that indicate CsA and FK506 operate as prodrugs are reviewed: they bind endogenous intracellular receptors, the immunophilins, and the resulting complex targets the protein phosphatase, calcineurin, to exert the immunosuppressive effect.
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Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation
TL;DR: It is reported here that overexpression of calcineurin in Jurkat cells renders them more resistant to the effects of CsA and FK506 and augments both NFAT- and NFIL2A-dependent transcription.
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Redox regulation of fos and jun DNA-binding activity in vitro
TL;DR: DNA binding of the Fos-Jun heterodimer was modulated by reduction-oxidation of a single conserved cysteine residue in the DNA-binding domains of the two proteins, suggesting that transcriptional activity mediated by AP-1 binding factors may be regulated by a redox mechanism.
Journal ArticleDOI
Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A.
TL;DR: NF-AT is formed when a signal from the antigen receptor induces a pre-existing cytoplasmic subunit to translocate to the nucleus and combine with a newly synthesized nuclear subunit of NF-AT, forming a inhibitory complex between the drug and isomerase.
Journal ArticleDOI
Identification of a putative regulator of early T cell activation genes
TL;DR: In this article, the authors used functional sequences of the T cell activation-specific enhancer of interleukin-2 (IL-2) to investigate the role of the antigen receptor-dependent regulation of early T-cell activation genes.