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They control the activity of thousands of genes during immune responses. Although their structure and function show numerous things in common, their expression and activity differ markedly in most types of lymphocytes. Over the last 40 years, the work of our laboratory revealed a strong inducible transcription of the Nfatc1 gene upon lymphocyte (co-)activation, compared to the \u2018tonic\u2019 transcription of Nfatc2. This leads to the inducible expression of a short NFATc1 isoform that we designated as NFATc1\/\u03b1A, which differs from longer NFATc1 proteins and NFATc2 by an individual N-terminal \u2018\u03b1\u2019 peptide and the absence of a C-terminal peptide of approximately 250 amino acid residues. While comprehensive experimental studies led to the conclusion that NFATc2 supports (i) apoptosis, (ii) the induction of anergy, and (iii) the \u2018exhaustion\u2019 of peripheral T cells, opposite conclusions can be derived from our studies of NFATc1\/\u03b1A. This view on the \u2018two faces\u2019 of NFAT transcription factors will be presented in this review and discussed in the role of NFATs in cancerogenesis.<\/jats:p>","DOI":"10.3390\/biom16060757","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T12:14:52Z","timestamp":1779452092000},"page":"757","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Two Faces of NFAT Transcription Factors in Lymphocytes\u2014A Personal Account"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1458-3767","authenticated-orcid":false,"given":"Edgar","family":"Serfling","sequence":"first","affiliation":[{"name":"Department of Molecular Pathology, Institute of Pathology, University of W\u00fcrzburg, Josef-Schneider-Str. 2, 97080 W\u00fcrzburg, Germany"},{"name":"Comprehensive Cancer Center Mainfranken, University of W\u00fcrzburg, Josef Schneider-Str. 6, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref_1","first-page":"1715","article-title":"Characterization of antigen receptor response elements within the interleukin-2 enhancer","volume":"8","author":"Durand","year":"1988","journal-title":"Mol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1002\/j.1460-2075.1989.tb03399.x","article-title":"Ubiquitous and lymphocyte-specific factors are involved in the induction of the mouse interleukin 2 gene in T lymphocytes","volume":"8","author":"Serfling","year":"1989","journal-title":"EMBO J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1126\/science.2595372","article-title":"Cyclosporin A specifically inhibits function of nuclear proteins involved in T cell activation","volume":"246","author":"Emmel","year":"1989","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1002\/j.1460-2075.1990.tb07433.x","article-title":"Cyclosporin A suppresses the expression of the interleukin 2 gene by inhibiting the binding of lymphocyte-specific factors to the IL-2 enhancer","volume":"9","author":"Randak","year":"1990","journal-title":"EMBO J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/0092-8674(86)90807-X","article-title":"Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism","volume":"47","author":"Sen","year":"1986","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1093\/nar\/19.1.61","article-title":"The immunosuppressives FK 506 and cyclosporin A inhibit the generation of protein factors binding to the two purine boxes of the interleukin 2 enhancer","volume":"19","author":"Brabletz","year":"1991","journal-title":"Nucleic Acids Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1111\/ctr.12072","article-title":"Hartmann Stahelin (1925\u20132011) and the contested history of cyclosporin A","volume":"27","author":"Cheng","year":"2013","journal-title":"Clin. Transplant."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/ctr.12136","article-title":"Comment on \u201cHartman Stahelin (1925\u20132011) and the contested history of cyclosporine A)\u201d","volume":"27","author":"Morris","year":"2013","journal-title":"Clin. Transplant."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1126\/science.6407111","article-title":"Drug transforms transplant medicine","volume":"221","author":"Kolata","year":"1983","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/0092-8674(91)90124-H","article-title":"Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes","volume":"66","author":"Liu","year":"1991","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1038\/357692a0","article-title":"FK-506- and CsA-sensitive activation of the interleukin-2 promoter by calcineurin","volume":"357","author":"Tamura","year":"1992","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/357695a0","article-title":"Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation","volume":"357","author":"Clipstone","year":"1992","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1093\/nar\/20.11.2657","article-title":"The weak, fine-tuned binding of ubiquitous transcription factors to the Il-2 enhancer contributes to its T cell-restricted activity","volume":"20","author":"Hentsch","year":"1992","journal-title":"Nucleic Acids Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/ni0109-3","article-title":"Signaling to gene expression: Calcium, calcineurin and NFAT","volume":"10","author":"Rao","year":"2009","journal-title":"Nat. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1126\/science.8235597","article-title":"Isolation of the cyclosporin-sensitive T cell transcription factor NFATp","volume":"262","author":"McCaffrey","year":"1993","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/369497a0","article-title":"NF-AT components define a family of transcription factors targeted in T-cell activation","volume":"369","author":"Northrop","year":"1994","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/1074-7613(95)90027-6","article-title":"Isolation of two new members of the NF-AT gene family and functional characterization of the NF-AT proteins","volume":"2","author":"Hoey","year":"1995","journal-title":"Immunity"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.1128\/MCB.15.5.2697","article-title":"NFATx, a novel member of the nuclear factor of activated T cells family that is expressed predominantly in the thymus","volume":"15","author":"Masuda","year":"1995","journal-title":"Mol. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/385172a0","article-title":"Unusual Rel-like architecture in the DNA-binding domain of the transcription factor NFATc","volume":"385","author":"Wolfe","year":"1997","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/S1074-7613(00)80051-5","article-title":"CBP\/p300 integrates Raf\/Rac-signaling pathways in the transcriptional induction of NF-ATc during T cell activation","volume":"10","author":"Avots","year":"1999","journal-title":"Immunity"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"10935","DOI":"10.1074\/jbc.M900465200","article-title":"Sumoylation of the transcription factor NFATc1 leads to its subnuclear relocalization and interleukin-2 repression by histone deacetylase","volume":"284","author":"Nayak","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7130","DOI":"10.1073\/pnas.97.13.7130","article-title":"A second calcineurin binding site on the NFAT regulatory domain","volume":"97","author":"Park","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1101\/gad.1102703","article-title":"Transcriptional regulation by calcium, calcineurin, and NFAT","volume":"17","author":"Hogan","year":"2003","journal-title":"Genes Dev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/S1097-2765(00)00053-8","article-title":"Concerted dephosphorylation of the transcription factor NFAT1 induces a conformational switch that regulates transcriptional activity","volume":"6","author":"Okamura","year":"2000","journal-title":"Mol. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7214","DOI":"10.1073\/pnas.96.13.7214","article-title":"NFAT5, a constitutively nuclear NFAT protein that does not cooperate with Fos and Jun","volume":"96","author":"Aramburu","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.ygeno.2008.06.011","article-title":"Alternative splicing and expression of human and mouse NFAT genes","volume":"92","author":"Vihma","year":"2008","journal-title":"Genomics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/1478-811X-10-16","article-title":"NFATc1\/alphaA: The other Face of NFAT Factors in Lymphocytes","volume":"10","author":"Serfling","year":"2012","journal-title":"Cell Commun. Signal"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/32419","article-title":"Role of the NF-ATc transcription factor in morphogenesis of cardiac valves and septum","volume":"392","author":"Timmerman","year":"1998","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/32426","article-title":"The transcription factor NF-ATc is essential for cardiac valve formation","volume":"392","author":"Ranger","year":"1998","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S1074-7613(00)80465-3","article-title":"Delayed lymphoid repopulation with defects in IL-4-driven responses produced by inactivation of NF-ATc","volume":"8","author":"Ranger","year":"1998","journal-title":"Immunity"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S1074-7613(00)80464-1","article-title":"The transcription factor NF-ATc1 regulates lymphocyte proliferation and Th2 cytokine production","volume":"8","author":"Yoshida","year":"1998","journal-title":"Immunity"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1002\/(SICI)1521-4141(199808)28:08<2456::AID-IMMU2456>3.0.CO;2-9","article-title":"Retarded thymic involution and massive germinal center formation in NF-ATp-deficient mice","volume":"28","author":"Schuh","year":"1998","journal-title":"Eur. J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4103","DOI":"10.1073\/pnas.0407691102","article-title":"De novo generation of antigen-specific CD4+CD25+ regulatory T cells from human CD4+CD25\u2212 cells","volume":"102","author":"Walker","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.cell.2008.05.009","article-title":"Regulatory T cells and immune tolerance","volume":"133","author":"Sakaguchi","year":"2008","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1084\/jem.20062129","article-title":"Cyclic adenosine monophosphate is a key component of regulatory T cell-mediated suppression","volume":"204","author":"Bopp","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2480","DOI":"10.1073\/pnas.1009463108","article-title":"Regulatory T cells facilitate the nuclear accumulation of inducible cAMP early repressor (ICER) and suppress nuclear factor of activated T cell c1 (NFATc1)","volume":"108","author":"Vaeth","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/ni904","article-title":"Foxp3 programs the development and function of CD4+CD25+ regulatory T cells","volume":"4","author":"Fontenot","year":"2003","journal-title":"Nat. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.cell.2006.05.042","article-title":"FOXP3 controls regulatory T cell function through cooperation with NFAT","volume":"126","author":"Wu","year":"2006","journal-title":"Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1084\/jem.20041538","article-title":"NFATc2 and NFATc3 transcription factors play a crucial role in suppression of CD4+ T lymphocytes by CD4+ CD25+ regulatory T cells","volume":"201","author":"Bopp","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"16258","DOI":"10.1073\/pnas.1203870109","article-title":"Dependence on nuclear factor of activated T-cells (NFAT) levels discriminates conventional T cells from Foxp3+ regulatory T cells","volume":"109","author":"Vaeth","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"RP88874","DOI":"10.7554\/eLife.88874","article-title":"Sustained store-operated calcium entry utilizing activated chromatin state leads to instability in iTregs","volume":"12","author":"Lyu","year":"2023","journal-title":"eLife"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"991","DOI":"10.15252\/embr.201338233","article-title":"Regulatory T cells suppress CD4+ T cells through NFAT-dependent transcriptional mechanisms","volume":"15","author":"Shin","year":"2014","journal-title":"EMBO Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1146\/annurev.immunol.21.120601.141110","article-title":"T cell anergy","volume":"21","author":"Schwartz","year":"2003","journal-title":"Annu. Rev. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/j.1600-065X.2009.00817.x","article-title":"Regulation of T-cell tolerance by calcium\/NFAT signaling","volume":"231","author":"Baine","year":"2009","journal-title":"Immunol. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/S0092-8674(02)00767-5","article-title":"Transcriptional mechanisms underlying lymphocyte tolerance","volume":"109","author":"Macian","year":"2002","journal-title":"Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1038\/nsb975","article-title":"An asymmetric NFAT1 dimer on a pseudo-palindromic kappa B-like DNA site","volume":"10","author":"Jin","year":"2003","journal-title":"Nat. Struct. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1038\/nsb981","article-title":"Structure of NFAT1 bound as a dimer to the HIV-1 LTR kappa B element","volume":"10","author":"Giffin","year":"2003","journal-title":"Nat. Struct. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1126\/science.1702903","article-title":"Association of B cell antigen receptor with protein tyrosine kinase Lyn","volume":"251","author":"Yamanashi","year":"1991","journal-title":"Science"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1038\/s41467-017-00830-y","article-title":"NFAT2 is a critical regulator of the anergic phenotype in chronic lymphocytic leukaemia","volume":"8","author":"Marklin","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.immuni.2006.10.010","article-title":"Antigen-receptor signaling to nuclear factor kappa B","volume":"25","author":"Ghosh","year":"2006","journal-title":"Immunity"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1084\/jem.20100945","article-title":"NFATc1 affects mouse splenic B cell function by controlling the calcineurin\u2014NFAT signaling network","volume":"208","author":"Bhattacharyya","year":"2011","journal-title":"J. Exp. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.4049\/jimmunol.1201591","article-title":"NFATc1 induction in peripheral T and B lymphocytes","volume":"190","author":"Hock","year":"2013","journal-title":"J. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Muhammad, K., Rudolf, R., Pham, D.A.T., Klein-Hessling, S., Takata, K., Matsushita, N., Ellenrieder, V., Kondo, E., and Serfling, E. (2018). Induction of Short NFATc1\/alphaA Isoform Interferes with Peripheral B Cell Differentiation. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00032"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/S1074-7613(00)80253-8","article-title":"Hyperproliferation and dysregulation of IL-4 expression in NF-ATp-deficient mice","volume":"4","author":"Hodge","year":"1996","journal-title":"Immunity"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/immu.200390000","article-title":"NF-ATc2 induces apoptosis in Burkitt\u2019s lymphoma cells through signaling via the B cell antigen receptor","volume":"33","author":"Kondo","year":"2003","journal-title":"Eur. J. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"11841","DOI":"10.1038\/ncomms11841","article-title":"A threshold level of NFATc1 activity facilitates thymocyte differentiation and opposes notch-driven leukaemia development","volume":"7","author":"Rudolf","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/S1074-7613(02)00329-1","article-title":"Autoregulation of NFATc1\/A expression facilitates effector T cells to escape from rapid apoptosis","volume":"16","author":"Chuvpilo","year":"2002","journal-title":"Immunity"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/ni.3706","article-title":"Epigenetic landscapes reveal transcription factors that regulate CD8(+) T cell differentiation","volume":"18","author":"Yu","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2007.02.005","article-title":"Chromatin modifications and their function","volume":"128","author":"Kouzarides","year":"2007","journal-title":"Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/s41467-017-00612-6","article-title":"NFATc1 controls the cytotoxicity of CD8(+) T cells","volume":"8","author":"Muhammad","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5427","DOI":"10.1038\/sj.onc.1205600","article-title":"CpG island hypermethylation and tumor suppressor genes: A booming present, a brighter future","volume":"21","author":"Esteller","year":"2002","journal-title":"Oncogene"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.4049\/jimmunol.179.2.1096","article-title":"A Costimulation-Initiated Signaling Pathway Regulates NFATc1 Transcription in T Lymphocytes","volume":"179","author":"Nurieva","year":"2007","journal-title":"J. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S1074-7613(00)80026-6","article-title":"Alternative polyadenylation events contribute to the induction of NF-ATc in effector T cells","volume":"10","author":"Chuvpilo","year":"1999","journal-title":"Immunity"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1093\/nar\/25.13.2547","article-title":"Alternative poly(A) site selection in complex transcription units: Means to an end?","volume":"25","author":"Veraldi","year":"1997","journal-title":"Nucleic Acids Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s41586-023-06922-8","article-title":"Affinity-optimizing enhancer variants disrupt development","volume":"626","author":"Lim","year":"2024","journal-title":"Nature"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/0092-8674(86)90660-4","article-title":"Regulation of human interleukin-2 gene: Functional DNA sequences in the 5\u2032 flanking region for the gene expression in activated T lymphocytes","volume":"46","author":"Fujita","year":"1986","journal-title":"Cell"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/0167-4781(95)00112-T","article-title":"The architecture of the interleukin-2 promoter: A reflection of T lymphocyte activation","volume":"1263","author":"Serfling","year":"1995","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"6299","DOI":"10.1128\/MCB.15.11.6299","article-title":"Novel NFAT sites that mediate activation of the interleukin-2 promoter in response to T-cell receptor stimulation","volume":"15","author":"Rooney","year":"1995","journal-title":"Mol. Cell Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S1074-7613(00)80424-0","article-title":"A T cell-specific enhancer in the interleukin-3 locus is activated cooperatively by Oct and NFAT elements within a DNase I-hypersensitive site","volume":"6","author":"Duncliffe","year":"1997","journal-title":"Immunity"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1128\/MCB.15.4.2071","article-title":"Human granulocyte-macrophage colony-stimulating factor enhancer function is associated with cooperative interactions between AP-1 and NFATp\/c","volume":"15","author":"Cockerill","year":"1995","journal-title":"Mol. Cell. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5694","DOI":"10.1093\/nar\/21.24.5694","article-title":"Multiple closely-linked NFAT\/octamer and HMG I(Y) binding sites are part of the interleukin-4 promoter","volume":"21","author":"Chuvpilo","year":"1993","journal-title":"Nucleic Acids Res."},{"key":"ref_72","first-page":"4793","article-title":"Identification of cis-acting regulatory elements controlling interleukin-4 gene expression in T cells: Roles for NF-Y and NF-ATc","volume":"13","author":"Szabo","year":"1993","journal-title":"Mol. Cell. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/1074-7613(95)90028-4","article-title":"Coordinate and cooperative roles for NF-AT and AP-1 in the regulation of the murine IL-4 gene","volume":"2","author":"Rooney","year":"1995","journal-title":"Immunity"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"17541","DOI":"10.1074\/jbc.270.29.17541","article-title":"Definition of cis-regulatory elements of the mouse interleukin-5 gene promoter. Involvement of nuclear factor of activated T cell-related factors in interleukin-5 expression","volume":"270","author":"Lee","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2956","DOI":"10.4049\/jimmunol.170.6.2956","article-title":"Protein kinase A regulates GATA-3-dependent activation of IL-5 gene expression in Th2 cells","volume":"170","author":"Jha","year":"2003","journal-title":"J. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1128\/MCB.16.2.459","article-title":"Tumor necrosis factor alpha gene regulation in activated T cells involves ATF-2\/Jun and NFATp","volume":"16","author":"Tsai","year":"1996","journal-title":"Mol. Cell Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5232","DOI":"10.1128\/MCB.16.10.5232","article-title":"Cell-type-specific regulation of the human tumor necrosis factor alpha gene in B cells and T cells by NFATp and ATF-2\/JUN","volume":"16","author":"Tsai","year":"1996","journal-title":"Mol. Cell. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"34775","DOI":"10.1074\/jbc.273.52.34775","article-title":"The roles of nuclear factor of activated T cells and ying-yang 1 in activation-induced expression of the interferon-gamma promoter in T cells","volume":"273","author":"Sweetser","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1182\/blood.V98.5.1480","article-title":"Regulation of interferon-gamma gene expression by nuclear factor of activated T cells","volume":"98","author":"Kiani","year":"2001","journal-title":"Blood"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"25291","DOI":"10.1074\/jbc.M501459200","article-title":"Calcium-dependent activation of interleukin-21 gene expression in T cells","volume":"280","author":"Kim","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"52762","DOI":"10.1074\/jbc.M405764200","article-title":"Crucial role for nuclear factor of activated T cells in T cell receptor-mediated regulation of human interleukin-17","volume":"279","author":"Liu","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_82","first-page":"2159","article-title":"Interleukin-2 transcription is regulated in vivo at the level of coordinated binding of both constitutive and regulated factors","volume":"14","author":"Garrity","year":"1994","journal-title":"Mol. Cell Biol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Podtschaske, M., Benary, U., Zwinger, S., H\u00f6fer, T., Radbruch, A., and Baumgrass, R. (2007). Digital NFATc2 activation per cell transforms graded T cell receptor activation into an all-or-none IL-2 expression. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0000935"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.4049\/jimmunol.166.3.1730","article-title":"A new regulatory region of the IL-2 locus that confers position-independent transgene expression","volume":"166","author":"Yui","year":"2001","journal-title":"J. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3200","DOI":"10.1093\/nar\/gki637","article-title":"Cell-type-specific epigenetic marking of the IL2 gene at a distal cis-regulatory region in competent, nontranscribing T-cells","volume":"33","author":"Adachi","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S1074-7613(00)80182-X","article-title":"Sequential involvement of NFAT and Egr transcription factors in FasL regulation","volume":"12","author":"Rengarajan","year":"2000","journal-title":"Immunity"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3744","DOI":"10.1128\/MCB.18.7.3744","article-title":"Cyclosporin A-sensitive transcription factor Egr-3 regulates Fas ligand expression","volume":"18","author":"Mittelstadt","year":"1998","journal-title":"Mol. Cell Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3222","DOI":"10.1074\/jbc.274.5.3222","article-title":"Role of Egr-2 in up-regulation of Fas ligand in normal T cells and aberrant double-negative lpr and gld T cells","volume":"274","author":"Mittelstadt","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/j.immuni.2017.11.021","article-title":"Transcription Factor IRF4 Promotes CD8(+) T Cell Exhaustion and Limits the Development of Memory-like T Cells during Chronic Infection","volume":"47","author":"Man","year":"2017","journal-title":"Immunity"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S1074-7613(03)00179-1","article-title":"Regulation of the Th2 cytokine locus by a locus control region","volume":"19","author":"Lee","year":"2003","journal-title":"Immunity"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1038\/ni1115","article-title":"Long-range intrachromosomal interactions in the T helper type 2 cytokine locus","volume":"5","author":"Spilianakis","year":"2004","journal-title":"Nat. Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/ni1148","article-title":"Hypersensitive site 7 of the TH2 locus control region is essential for expressing TH2 cytokine genes and for long-range intrachromosomal interactions","volume":"6","author":"Lee","year":"2005","journal-title":"Nat. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/S1074-7613(00)80215-0","article-title":"Cell-type-restricted binding of the transcription factor NFAT to a distal IL-4 enhancer in vivo","volume":"12","author":"Agarwal","year":"2000","journal-title":"Immunity"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/ni744","article-title":"NFATc2 and NFATc3 regulate T(H)2 differentiation and modulate TCR-responsiveness of naive T(H)cells","volume":"3","author":"Rengarajan","year":"2002","journal-title":"Nat. Immunol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"4459","DOI":"10.4049\/jimmunol.1201915","article-title":"The inducible tissue-specific expression of the human IL-3\/GM-CSF locus is controlled by a complex array of developmentally regulated enhancers","volume":"189","author":"Baxter","year":"2012","journal-title":"J. Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1128\/MCB.01411-08","article-title":"A conserved insulator that recruits CTCF and cohesin exists between the closely related but divergently regulated interleukin-3 and granulocyte-macrophage colony-stimulating factor genes","volume":"29","author":"Bowers","year":"2009","journal-title":"Mol. Cell Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.4049\/jimmunol.169.4.1876","article-title":"The human IL-3 locus is regulated cooperatively by two NFAT-dependent enhancers that have distinct tissue-specific activities","volume":"169","author":"Hawwari","year":"2002","journal-title":"J. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e2199","DOI":"10.1038\/cddis.2016.97","article-title":"Cell cycle and apoptosis regulation by NFAT transcription factors: New roles for an old player","volume":"7","author":"Mognol","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1006\/jmbi.1999.2684","article-title":"Recognition of NFATp\/AP-1 composite elements within genes induced upon the activation of immune cells","volume":"288","author":"Kel","year":"1999","journal-title":"J. Mol. Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/356801a0","article-title":"Nuclear factor of activated T cells contains Fos and Jun","volume":"356","author":"Jain","year":"1992","journal-title":"Nature"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/0092-8674(87)90611-8","article-title":"Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor","volume":"49","author":"Angel","year":"1987","journal-title":"Cell"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1126\/science.3289117","article-title":"The leucine zipper: A hypothetical structure common to a new class of DNA binding proteins","volume":"240","author":"Landschulz","year":"1988","journal-title":"Science"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.1038\/sj.onc.1204385","article-title":"Close encounters of many kinds: Fos-Jun interactions that mediate transcription regulatory specificity","volume":"20","author":"Chinenov","year":"2001","journal-title":"Oncogene"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1038\/nature07885","article-title":"Design of protein-interaction specificity gives selective bZIP-binding peptides","volume":"458","author":"Grigoryan","year":"2009","journal-title":"Nature"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"837","DOI":"10.4049\/jimmunol.151.2.837","article-title":"Analysis of the preexisting and nuclear forms of nuclear factor of activated T cells","volume":"151","author":"Jain","year":"1993","journal-title":"J. Immunol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"4783","DOI":"10.1093\/emboj\/19.17.4783","article-title":"Gene expression elicited by NFAT in the presence or absence of cooperative recruitment of Fos and Jun","volume":"19","author":"Macian","year":"2000","journal-title":"EMBO J."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/32100","article-title":"Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA","volume":"392","author":"Chen","year":"1998","journal-title":"Nature"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/ni1047","article-title":"Calcineurin imposes T cell unresponsiveness through targeted proteolysis of signaling proteins","volume":"5","author":"Heissmeyer","year":"2004","journal-title":"Nat. Immunol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"24172","DOI":"10.1074\/jbc.M116.739326","article-title":"Identification of Novel Nuclear Factor of Activated T Cell (NFAT)-associated Proteins in T Cells","volume":"291","author":"Gabriel","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"11724","DOI":"10.1038\/ncomms11724","article-title":"NFATc1 supports imiquimod-induced skin inflammation by suppressing IL-10 synthesis in B cells","volume":"7","author":"Alrefai","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"34967","DOI":"10.1074\/jbc.M205048200","article-title":"Correlation of transcriptional repression by p21(SNFT) with changes in DNA.NF-AT complex interactions","volume":"277","author":"Bower","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nri3470","article-title":"Specificity through cooperation: BATF-IRF interactions control immune-regulatory networks","volume":"13","author":"Murphy","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/ni.2834","article-title":"The transcription factor BATF operates as an essential differentiation checkpoint in early effector CD8+ T cells","volume":"15","author":"Kurachi","year":"2014","journal-title":"Nat. Immunol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1084\/jem.20011128","article-title":"Interferon regulatory factor 4 (IRF4) interacts with NFATc2 to modulate interleukin 4 gene expression","volume":"195","author":"Rengarajan","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1038\/s41590-021-00964-8","article-title":"BATF and IRF4 cooperate to counter exhaustion in tumor-infiltrating CAR T cells","volume":"22","author":"Seo","year":"2021","journal-title":"Nat. Immunol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S0092-8674(00)81299-4","article-title":"The proto-oncogene c-maf is responsible for tissue-specific expression of interleukin-4","volume":"85","author":"Ho","year":"1996","journal-title":"Cell"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1084\/jem.187.12.2031","article-title":"Nuclear factor of activated T cells (NFAT)-dependent transactivation regulated by the coactivators p300\/CREB-binding protein (CBP)","volume":"187","author":"Rao","year":"1998","journal-title":"J. Exp. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"9544","DOI":"10.1074\/jbc.273.16.9544","article-title":"Role of transcriptional repressor ICER in cyclic AMP-mediated attenuation of cytokine gene expression in human thymocytes","volume":"273","author":"Bodor","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1093\/nar\/gkg186","article-title":"Early growth response proteins (EGR) and nuclear factors of activated T cells (NFAT) form heterodimers and regulate proinflammatory cytokine gene expression","volume":"31","author":"Decker","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"31030","DOI":"10.1074\/jbc.M805929200","article-title":"Cyclic AMP-induced chromatin changes support the NFATc-mediated recruitment of GATA-3 to the interleukin 5 promoter","volume":"283","author":"Bopp","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"4698","DOI":"10.1038\/s41467-019-12680-x","article-title":"NFAT primes the human RORC locus for RORgammat expression in CD4(+) T cells","volume":"10","author":"Rybczynska","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Lee, J.U., Kim, L.K., and Choi, J.M. (2018). Revisiting the Concept of Targeting NFAT to Control T Cell Immunity and Autoimmune Diseases. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02747"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"2989","DOI":"10.1182\/blood-2009-10-233585","article-title":"NFAT pulls the strings during CD4+ T helper cell effector functions","volume":"115","author":"Baier","year":"2010","journal-title":"Blood"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/0092-8674(91)90123-G","article-title":"Two cytoplasmic candidates for immunophilin action are revealed by affinity for a new cyclophilin: One in the presence and one in the absence of CsA","volume":"66","author":"Friedman","year":"1991","journal-title":"Cell"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"S67","DOI":"10.1016\/S0092-8674(02)00699-2","article-title":"NFAT signaling: Choreographing the social lives of cells","volume":"109","author":"Crabtree","year":"2002","journal-title":"Cell"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1084\/jem.183.2.413","article-title":"T cell responses in calcineurin A alpha-deficient mice","volume":"183","author":"Zhang","year":"1996","journal-title":"J. Exp. Med."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"9398","DOI":"10.1073\/pnas.152665399","article-title":"Defective T cell development and function in calcineurin A beta-deficient mice","volume":"99","author":"Bueno","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1002\/1521-4141(200205)32:5<1223::AID-IMMU1223>3.0.CO;2-5","article-title":"Calcineurin Aalpha plays an exclusive role in TCR signaling in mature but not in immature T cells","volume":"32","author":"Chan","year":"2002","journal-title":"Eur. J. Immunol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S1074-7613(04)00052-4","article-title":"Calcineurin B1 is essential for positive but not negative selection during thymocyte development","volume":"20","author":"Neilson","year":"2004","journal-title":"Immunity"},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Mencarelli, A., Vacca, M., Khameneh, H.J., Acerbi, E., Tay, A., Zolezzi, F., Poidinger, M., and Mortellaro, A. (2018). Calcineurin B in CD4(+) T Cells Prevents Autoimmune Colitis by Negatively Regulating the JAK\/STAT Pathway. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00261"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/S1097-2765(00)80063-5","article-title":"Selective inhibition of NFAT activation by a peptide spanning the calcineurin targeting site of NFAT","volume":"1","author":"Aramburu","year":"1998","journal-title":"Mol. Cell"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1126\/science.285.5436.2129","article-title":"Affinity-driven peptide selection of an NFAT inhibitor more selective than cyclosporin A","volume":"285","author":"Aramburu","year":"1999","journal-title":"Science"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.molcel.2020.06.029","article-title":"Systematic Discovery of Short Linear Motifs Decodes Calcineurin Phosphatase Signaling","volume":"79","author":"Wigington","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1126\/science.1115901","article-title":"A strategy for probing the function of noncoding RNAs finds a repressor of NFAT","volume":"309","author":"Willingham","year":"2005","journal-title":"Science"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1038\/ni.2113","article-title":"The kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease","volume":"12","author":"Liu","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1126\/science.1151227","article-title":"NFAT binding and regulation of T cell activation by the cytoplasmic scaffolding Homer proteins","volume":"319","author":"Huang","year":"2008","journal-title":"Science"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"11381","DOI":"10.1073\/pnas.1019711108","article-title":"Dephosphorylation of the nuclear factor of activated T cells (NFAT) transcription factor is regulated by an RNA-protein scaffold complex","volume":"108","author":"Sharma","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"4184","DOI":"10.1128\/MCB.24.10.4184-4195.2004","article-title":"A conserved docking motif for CK1 binding controls the nuclear localization of NFAT1","volume":"24","author":"Okamura","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1038\/nri2152","article-title":"Calcium signalling in lymphocyte activation and disease","volume":"7","author":"Feske","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1146\/annurev.immunol.021908.132550","article-title":"Molecular basis of calcium signaling in lymphocytes: STIM and ORAI","volume":"28","author":"Hogan","year":"2010","journal-title":"Annu. Rev. Immunol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/ni.2507","article-title":"An alternative NFAT-activation pathway mediated by IL-7 is critical for early thymocyte development","volume":"14","author":"Patra","year":"2013","journal-title":"Nat. Immunol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"5559","DOI":"10.4049\/jimmunol.1302293","article-title":"Unique features of naive CD8+ T cell activation by IL-2","volume":"191","author":"Cho","year":"2013","journal-title":"J. Immunol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.immuni.2017.09.003","article-title":"Store-Operated Ca(2+) Entry Controls Clonal Expansion of T Cells through Metabolic Reprogramming","volume":"47","author":"Vaeth","year":"2017","journal-title":"Immunity"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1182\/blood-2007-06-096297","article-title":"IL-7 promotes Glut1 trafficking and glucose uptake via STAT5-mediated activation of Akt to support T-cell survival","volume":"111","author":"Wofford","year":"2008","journal-title":"Blood"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1038\/s41577-021-00537-8","article-title":"CD8(+) T cell metabolism in infection and cancer","volume":"21","author":"Scharping","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"4661","DOI":"10.4049\/jimmunol.172.8.4661","article-title":"Regulation of T lymphocyte metabolism","volume":"172","author":"Frauwirth","year":"2004","journal-title":"J. Immunol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1242454","DOI":"10.1126\/science.1242454","article-title":"Fueling immunity: Insights into metabolism and lymphocyte function","volume":"342","author":"Pearce","year":"2013","journal-title":"Science"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/nri.2016.70","article-title":"A guide to immunometabolism for immunologists","volume":"16","author":"Kishton","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1016\/j.cell.2013.05.016","article-title":"Posttranscriptional control of T cell effector function by aerobic glycolysis","volume":"153","author":"Chang","year":"2013","journal-title":"Cell"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.immuni.2015.01.006","article-title":"The transcription factor NFAT promotes exhaustion of activated CD8(+) T cells","volume":"42","author":"Martinez","year":"2015","journal-title":"Immunity"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1158\/2159-8290.CD-13-0593","article-title":"Inflammation-induced NFATc1-STAT3 transcription complex promotes pancreatic cancer initiation by KrasG12D","volume":"4","author":"Baumgart","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1182\/blood.2022018303","article-title":"Biallelic NFATC1 mutations cause an inborn error of immunity with impaired CD8+ T-cell function and perturbed glycolysis","volume":"142","author":"Bal","year":"2023","journal-title":"Blood"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.immuni.2009.07.009","article-title":"Differential expression of interleukin-17A and -17F is coupled to T cell receptor signaling via inducible T cell kinase","volume":"31","author":"Sahu","year":"2009","journal-title":"Immunity"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.cmet.2022.02.015","article-title":"The glucose transporter GLUT3 controls T helper 17 cell responses through glycolytic-epigenetic reprogramming","volume":"34","author":"Hochrein","year":"2022","journal-title":"Cell Metab."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"112583","DOI":"10.1016\/j.celrep.2023.112583","article-title":"Pyruvate metabolism controls chromatin remodeling during CD4(+) T cell activation","volume":"42","author":"Mocholi","year":"2023","journal-title":"Cell Rep."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/s41577-020-00478-8","article-title":"Redox regulation of immunometabolism","volume":"21","author":"Muri","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.immuni.2017.02.010","article-title":"Integrative Proteomics and Phosphoproteomics Profiling Reveals Dynamic Signaling Networks and Bioenergetics Pathways Underlying T Cell Activation","volume":"46","author":"Tan","year":"2017","journal-title":"Immunity"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.15252\/embj.201696151","article-title":"Cancer cell metabolism: The essential role of the nonessential amino acid, glutamine","volume":"36","author":"Zhang","year":"2017","journal-title":"EMBO J."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.it.2018.01.005","article-title":"Reactive Oxygen Species: Involvement in T Cell Signaling and Metabolism","volume":"39","author":"Franchina","year":"2018","journal-title":"Trends Immunol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.immuni.2012.10.020","article-title":"Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling","volume":"38","author":"Sena","year":"2013","journal-title":"Immunity"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/ni1096","article-title":"T cells express a phagocyte-type NADPH oxidase that is activated after T cell receptor stimulation","volume":"5","author":"Jackson","year":"2004","journal-title":"Nat. Immunol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1016\/j.celrep.2012.10.009","article-title":"T cell activation is driven by an ADP-dependent glucokinase linking enhanced glycolysis with mitochondrial reactive oxygen species generation","volume":"2","author":"Sauer","year":"2012","journal-title":"Cell Rep."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"6858","DOI":"10.1038\/s41467-023-42634-3","article-title":"Mitochondrial dysfunction promotes the transition of precursor to terminally exhausted T cells through HIF-1alpha-mediated glycolytic reprogramming","volume":"14","author":"Wu","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"260","DOI":"10.12688\/f1000research.13426.1","article-title":"NFAT control of immune function: New Frontiers for an Abiding Trooper","volume":"7","author":"Vaeth","year":"2018","journal-title":"F1000Res"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1097\/00007890-198701000-00008","article-title":"Cancers following cyclosporine therapy","volume":"43","author":"Penn","year":"1987","journal-title":"Transplantation"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1056\/NEJMra022137","article-title":"Skin cancers after organ transplantation","volume":"348","author":"Euvrard","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"D523","DOI":"10.1093\/nar\/gkh013","article-title":"RTCGD: Retroviral tagged cancer gene database","volume":"32","author":"Akagi","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.it.2006.08.005","article-title":"NFATc1 autoregulation: A crucial step for cell-fate determination","volume":"27","author":"Serfling","year":"2006","journal-title":"Trends Immunol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"3546","DOI":"10.1182\/blood-2005-02-0493","article-title":"A tumor-suppressor function for NFATc3 in T-cell lymphomagenesis by murine leukemia virus","volume":"106","author":"Glud","year":"2005","journal-title":"Blood"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1084\/jem.191.1.9","article-title":"The nuclear factor of activated T cells (NFAT) transcription factor NFATp (NFATc2) is a repressor of chondrogenesis","volume":"191","author":"Ranger","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"17246","DOI":"10.1074\/jbc.M300528200","article-title":"A constitutively active NFATc1 mutant induces a transformed phenotype in 3T3-L1 fibroblasts","volume":"278","author":"Neal","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"7168","DOI":"10.1128\/MCB.00256-08","article-title":"Dual roles for NFAT transcription factor genes as oncogenes and tumor suppressors","volume":"28","author":"Robbs","year":"2008","journal-title":"Mol. Cell Biol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1128\/MCB.00501-15","article-title":"NFAT2 Isoforms Differentially Regulate Gene Expression, Cell Death, and Transformation through Alternative N-Terminal Domains","volume":"36","author":"Lucena","year":"2016","journal-title":"Mol. Cell Biol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/nri2818","article-title":"NFAT, immunity and cancer: A transcription factor comes of age","volume":"10","author":"Muller","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"115167","DOI":"10.1016\/j.biopha.2023.115167","article-title":"NFAT signaling dysregulation in cancer: Emerging roles in cancer stem cells","volume":"165","author":"Lin","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Tie, X., Han, S., Meng, L., Wang, Y., and Wu, A. (2013). NFAT1 is highly expressed in, and regulates the invasion of, glioblastoma multiforme cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066008"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s12964-017-0210-1","article-title":"NFAT1-regulated IL6 signalling contributes to aggressive phenotypes of glioma","volume":"15","author":"Jiang","year":"2017","journal-title":"Cell Commun. Signal"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1475-2867-13-41","article-title":"Depleting NFAT1 expression inhibits the ability of invasion and migration of human lung cancer cells","volume":"13","author":"Liu","year":"2013","journal-title":"Cancer Cell Int."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1186\/s13046-017-0599-9","article-title":"The acid-sensing ion channel, ASIC2, promotes invasion and metastasis of colorectal cancer under acidosis by activating the calcineurin\/NFAT1 axis","volume":"36","author":"Zhou","year":"2017","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"3714","DOI":"10.1038\/sj.emboj.7601246","article-title":"Overexpression of c-myc in pancreatic cancer caused by ectopic activation of NFATc1 and the Ca2+\/calcineurin signaling pathway","volume":"25","author":"Buchholz","year":"2006","journal-title":"EMBO J."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"517","DOI":"10.15252\/embj.201489574","article-title":"Antithetical NFATc1-Sox2 and p53-miR200 signaling networks govern pancreatic cancer cell plasticity","volume":"34","author":"Singh","year":"2015","journal-title":"EMBO J."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.immuni.2020.04.014","article-title":"Developmental Relationships of Four Exhausted CD8(+) T Cell Subsets Reveals Underlying Transcriptional and Epigenetic Landscape Control Mechanisms","volume":"52","author":"Beltra","year":"2020","journal-title":"Immunity"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/ni.2035","article-title":"T cell exhaustion","volume":"12","author":"Wherry","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.immuni.2012.09.012","article-title":"The transcription factor NFAT exhibits signal memory during serial T cell interactions with antigen-presenting cells","volume":"38","author":"Marangoni","year":"2013","journal-title":"Immunity"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.immuni.2007.09.006","article-title":"Molecular signature of CD8+ T cell exhaustion during chronic viral infection","volume":"27","author":"Wherry","year":"2007","journal-title":"Immunity"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"3831","DOI":"10.4049\/jimmunol.179.6.3831","article-title":"Induction of the CTLA-4 gene in human lymphocytes is dependent on NFAT binding the proximal promoter","volume":"179","author":"Gibson","year":"2007","journal-title":"J. Immunol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"4832","DOI":"10.4049\/jimmunol.181.7.4832","article-title":"NFATc1 regulates PD-1 expression upon T cell activation","volume":"181","author":"Oestreich","year":"2008","journal-title":"J. Immunol."},{"key":"ref_188","unstructured":"Sampere-Birlanga, S., Klein-Hessling, S., Campillo Prados, M., Huang, A., Wu, H., Rosenwald, A., Kastenm\u00fcller, W., Serfling, E., Vaeth, M., and Berberich-Siebelt, F. (Cells, 2026). Non-redundant Functions of NFATc1 in Survival and NFATc2 in Generation of Exhausted CD8+ T Cells, Cells, submitted."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/j.cell.2015.08.016","article-title":"Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression","volume":"162","author":"Chang","year":"2015","journal-title":"Cell"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.cmet.2016.08.011","article-title":"LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells","volume":"24","author":"Brand","year":"2016","journal-title":"Cell Metab."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.it.2022.10.005","article-title":"Lactic acid and lactate: Revisiting the physiological roles in the tumor microenvironment","volume":"43","author":"Apostolova","year":"2022","journal-title":"Trends Immunol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1182\/blood-2006-07-035972","article-title":"Inhibitory effect of tumor cell-derived lactic acid on human T cells","volume":"109","author":"Fischer","year":"2007","journal-title":"Blood"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.semcancer.2022.12.001","article-title":"Targeting lactate metabolism for cancer immunotherapy\u2014A matter of precision","volume":"88","author":"Heuser","year":"2023","journal-title":"Semin. Cancer Biol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"e2253","DOI":"10.1038\/cddis.2016.105","article-title":"ROS homeostasis and metabolism: A dangerous liason in cancer cells","volume":"7","author":"Panieri","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1152\/physrev.2000.80.4.1483","article-title":"Calcineurin: Form and function","volume":"80","author":"Rusnak","year":"2000","journal-title":"Physiol. Rev."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/6\/757\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,24]],"date-time":"2026-05-24T04:11:27Z","timestamp":1779595887000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/6\/757"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,22]]},"references-count":195,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["biom16060757"],"URL":"https:\/\/doi.org\/10.3390\/biom16060757","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,22]]}}}