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Transcription factors of the NFAT family: regulation and function.
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. Expand
A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function
It is proposed that Orai1 is an essential component or regulator of the CRAC channel complex, which contains four putative transmembrane segments and is based on a novel protein that was identified in SCID patients. Expand
Transcriptional regulation by calcium, calcineurin, and NFAT.
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. Expand
Orai1 is an essential pore subunit of the CRAC channel
It is shown that Orai1 is a plasma membrane protein, and that CRAC channel function is sensitive to mutation of two conserved acidic residues in the transmembrane segments, which reduces Ca2+ influx, increases current carried by monovalent cations, and renders the channel permeable to Cs+. Expand
Molecular basis of calcium signaling in lymphocytes: STIM and ORAI.
Ca(2+) entry into cells of the peripheral immune system occurs through highly Ca(2+)-selective channels known as CRAC (calcium release-activated calcium) channels. CRAC channels are a veryExpand
Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T cell activation and tolerance
It is concluded that both STIM1 and STIM2 promote store-operated Ca2+ entry into T cells and fibroblasts and that STIM proteins are required for the development and function of regulatory T cells. Expand
Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA
The nuclear factor of activated T cells (NFAT) and the AP-1 heterodimer, Fos–Jun, cooperatively bind a composite DNA site and synergistically activate the expression of many immune-response genes. AExpand
Concerted dephosphorylation of the transcription factor NFAT1 induces a conformational switch that regulates transcriptional activity.
The data suggest that dephosphorylation promotes NFAT1 activation by increasing the probability of an active conformation, in a manner analogous to that by which depolarization increases the open probability of voltage-gated ion channels. Expand
Affinity-driven peptide selection of an NFAT inhibitor more selective than cyclosporin A.
Compounds that interfere selectively with the calcineurin-NFAT interaction without affecting calcineURin phosphatase activity may be useful as therapeutic agents that are less toxic than current drugs. Expand
Biochemical and Functional Characterization of Orai Proteins*
Orai1 is predominantly responsible for store-operated Ca2+ influx in human embryonic kidney 293 cells and human T cells and fibroblasts, although its paralogue Orai3 can partly compensate in the absence of functional ORAi1. Expand