Cited by 158Signaling Pathways in DiseaseCalpain Protease Function and RegulationNuclear Receptors and Signaling

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Calcineurin: a central controller of signalling in eukaryotes: Workshop on the Calcium/Calcineurin/NFAT Pathway: Regulation and Function

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Aramburu, José, Heitman, Joseph, Crabtree, Gerald R.·2004·The EMBO Reports

DOI 10.1038/sj.embor.7400133PMC PMC1299038

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A Calcineurin-Dependent Transcriptional Pathway for Cardiac Hypertrophy
Molkentin, J. D., Lu, J., Antos, C. L., Markham, B. E., Richardson, J. A., Robbins, J. M., Grant, S. R., & Olson, E. N. (1998) · Cell · doi:10.1016/s0092-8674(00)81573-1 · Cited by 2,566
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Calcineurin imposes T cell unresponsiveness through targeted proteolysis of signaling proteins
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L-type calcium channels and GSK-3 regulate the activity of NF-ATc4 in hippocampal neurons
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Self-citation
Forebrain-Specific Calcineurin Knockout Selectively Impairs Bidirectional Synaptic Plasticity and Working/Episodic-like Memory
Zeng, H., Chattarji, S., Barbarosie, M., Rondi-Reig, L., Philpot, B. D., Miyakawa, T., Bear, M. F., & Tonegawa, S. (2001) · Cell · doi:10.1016/s0092-8674(01)00585-2 · Cited by 498
Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia
Miyakawa, T., Leiter, L. M., Gerber, D. J., Gainetdinov, R. R., Sotnikova, T. D., Zeng, H., Caron, M. G., & Tonegawa, S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1432926100 · Cited by 489
Inducible and Reversible Enhancement of Learning, Memory, and Long-Term Potentiation by Genetic Inhibition of Calcineurin
Malleret, G., Haditsch, U., Genoux, D., Jones, M. W., Bliss, T. V. P., Vanhoose, A. M., Weitlauf, C., Kandel, E. R., Winder, D. G., & Mansuy, I. M. (2001) · Cell · doi:10.1016/s0092-8674(01)00264-1 · Cited by 470
Selective Inhibition of Vascular Endothelial Growth Factor–Mediated Angiogenesis by Cyclosporin a
Hernández, G., Volpert, O. V., Iñiguez, M. A., Lorenzo, E., Martı́nez-Martı́nez, S., Grau, R., Fresno, M., & Redondo, J. M. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.5.607 · Cited by 430
Signals Transduced by Ca2+/Calcineurin and NFATc3/c4 Pattern the Developing Vasculature
Graef, I. A., Chen, F., Chen, L., Kuo, A., & Crabtree, G. R. (2001) · Cell · doi:10.1016/s0092-8674(01)00396-8 · Cited by 421
Self-citation
Genetic and Pharmacological Evidence for a Novel, Intermediate Phase of Long-Term Potentiation Suppressed by Calcineurin
Winder, D. G., Mansuy, I. M., Osman, M., Moallem, T. M., & Kandel, E. R. (1998) · Cell · doi:10.1016/s0092-8674(00)80896-x · Cited by 350

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“Specific inhibitors of ORAI1 and CRAC channel function might have fewer unwanted adverse effects than cyclosporin A or FK506, because calcineurin function is crucial in many cell types and organs, whereas ORAI1 may have non-redundant functions only in a few cell types, including T cells, as judged by the phenotype in…”
Background
Reversible phosphorylation of Drp1 by cyclic AMP‐dependent protein kinase and calcineurin regulates mitochondrial fission and cell death
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“The serine/threonine phosphatase calcineurin is one of the main transducers of cytosolic calcium fluxes, with particularly important and well-characterized roles in immune cells and the nervous system (Aramburu et al, 2004).”
Background
The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A
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“As underscored by the drugs FK506 and cyclosporin, which have both immunosuppressive and antifungal activities by targeting the calcineurin pathway in humans and fungi, respectivel”
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“Calcineurin is a ubiquitously expressed serine/threonine phosphatase.(106) The best-characterized function of calcineurin is the regulation of nuclear factor of activated T cells (NFAT) signaling.”
Background
Calcineurin-Responsive Zinc Finger Transcription Factor CRZ1 of Botrytis cinerea Is Required for Growth, Development, and Full Virulence on Bean Plants
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“This compound mediates immunosuppression by inhibiting CaN-mediated dephosphorylation of NFAT, a transcription factor that regulates the expression of IL-2, which in turn regulates T-lymphocyte proliferation (Aramburu et al., 2004).”
Background
The podocyte as a direct target of immunosuppressive agents
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“Calcineurin is a serine/threonine phosphatase that is ubiquitously expressed in all mammalian tissues and tightly regulated by Ca/calmodulin [38].”
Background
GmHs1-1, encoding a calcineurin-like protein, controls hard-seededness in soybean
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“When activated by calcium, calcineurin, dephosphorylates NFAT, which translocates to the nucleus and activates genes that contribute to growth [160] or apoptosis [161], depending on the trigger.”
Background
Calcineurin controls drug tolerance, hyphal growth, and virulence in Candida dubliniensis
Chen, Y.-L., Brand, A., Morrison, E. L., Silao, F. G. S., Bigol, U. G., Malbas, F. F., Nett, J. E., Andes, D. R., Solis, N. V., Filler, S. G., et al. (2011) · Eukaryotic Cell · doi:10.1128/ec.00310-10 · Cited by 107
“highly conserved between yeasts and mammals (3).”
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Recent Approaches to Antifungal Therapy for Invasive Mycoses
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“TCR engagement results in the activation of the calmodulin-dependent phosphatase calcineurin, which binds to the N-terminus of NFAT and dephosphorylates multiple serine residues in the NFAT protein [80, 81].”
Background
Calcineurin Targets Involved in Stress Survival and Fungal Virulence
Hee-Soo, P., Chow, E. W. L., Fu, C., Soderblom, E. J., Moseley, M. A., Heitman, J., & Cardenas, M. E. (2016) · PLoS Pathogens · doi:10.1371/journal.ppat.1005873 · Cited by 94
“Calcineurin is a Ca/calmodulin-activatedserine/threonine-specificprotein phosphatase consisting of two subunits: a catalytic A subunit and a regulatory B subunit [22,23].”
BackgroundSelf-citation
Regulation of T‐cell tolerance by calcium/NFAT signaling
Baine, I. L., Abe, B. T., & Macián, F. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2009.00817.x · Cited by 95
“the calcium-regulated signaling in T cells (49).”
Brawn for Brains: The Role of MEF2 Proteins in the Developing Nervous System
Shalizi, A., & Bonni, A. (2005) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(05)69009-6 · Cited by 86
Calcineurin Regulation in Fungi and Beyond
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The podocyte as a direct target for treatment of glomerular disease?
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“These data combined show that different NFAT C-termini could potentially have functionally unique characteristics, emphasizing that although NFAT proteins may have redundancy in their functions, as can be concluded from knockout studies [47,48], the specific functions of different NFAT isoforms could have an impact on…”
Background
Functional characterization of the Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor
Santos, M., & de Larrinoa, I. F. (2005) · Current Genetics · doi:10.1007/s00294-005-0003-8 · Cited by 78
“Calcineurin is a serine and threonine-specific protein phosphatase specialized in the transduction of Ca2+- signals in eukaryotes (Aramburu et al. 2004).”
Background
Adaptation to environmental pH: integrating the Rim101 and calcineurin signal transduction pathways
Kullas, A. L., Martin, S. J., & Davis, D. (2007) · Molecular Microbiology · doi:10.1111/j.1365-2958.2007.05929.x · Cited by 75
“Calcineurin is a protein phosphatase conserved throughout eukaryotic evolution (Rusnak and Mertz, 2000; Aramburu et al., 2004).”
Background
Podocyte-targeted therapies — progress and future directions
Meliambro, K. A., He, C., & Campbell, K. N. (2024) · Nature Reviews Nephrology · doi:10.1038/s41581-024-00843-z · Cited by 87
“Calcineurin is a serine–threonine phosphatase that dephosphorylates nuclear factor of activated T cells (NFAT), leading to NFAT nuclear translocation and upregulation of the T cell-mediated immune response 179 .”
Genetic and pharmacological inhibition of calcineurin corrects the BDNF transport defect in Huntington's disease
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“It consists of a calmodulin-binding 60 kDa catalytic subunit, calcineurin A (CaNA), and an intrinsic Ca+2-binding 19 kDa regulatory subunit, calcineurin B (CaNB) [ 21-24 ].”
Background
HIV-1, Methamphetamine and Astrocyte Glutamate Regulation: Combined Excitotoxic Implications for Neuro-AIDS
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“NFAT activation requires translocation from the cytoplasm to the nucleus and is triggered by an intracellular Ca +2 /calmodulindependent phosphates, which links Ca 2+ signaling and NFAT-dependent gene transcription in astrocytes [28].”
Background
NF-κB regulates thrombin-induced ICAM-1 gene expression in cooperation with NFAT by binding to the intronic NF-κB site in the ICAM-1 gene
Xue, J., Thippegowda, P. B., Hu, G., Bachmaier, K., Christman, J. W., Malik, A. B., & Tiruppathì, C. (2009) · Physiological Genomics · doi:10.1152/physiolgenomics.00012.2009 · Cited by 75
Calmodulin-controlled spatial decoding of oscillatory Ca2+ signals by calcineurin
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“DOI: 10.7554/eLife.03765 2 of 22 Research article differentiation, and death, as well as gene expression, secretion, immune function, learning, and memory (reviewed in Rusnak and Mertz, 2000; Aramburu et al., 2004).”
Influential
Blockade of NFAT Activation by the Second Calcineurin Binding Site
Martı́nez-Martı́nez, S., Rodrı́guez, A., López-Maderuelo, D., Ortega‐Pérez, I., Vázquez, J., & Redondo, J. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m513885200 · Cited by 74
Calcium and Cell Death
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Calcineurin Inhibition at the Clinical Phase of Prion Disease Reduces Neurodegeneration, Improves Behavioral Alterations and Increases Animal Survival
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“implicated in immunological and inflammatory pathways [27], we”
Background
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“Although calcineurin has been reported to be implicated in a wide range of cellular processes such as cell cycle regulation, stress response, and apoptosis [51], how calcineurin contributes to the decision of cellular protection or commitment to cell death is still largely unknown and debatable [48].”
Background
SOCE induced calcium overload regulates autophagy in acute pancreatitis via calcineurin activation
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Background
Calcineurin Colocalizes with P-Bodies and Stress Granules during Thermal Stress in Cryptococcus neoformans
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“Calcineurin is a calcium-calmodulin-dependent serine/threonine-specific phosphatase consisting of a catalytic A subunit and a regulatory B subunit, both of which are essential for enzyme activity (2, 10).”
BackgroundSelf-citation
Loss-of-function and gain-of-function mutations in PPP3CA cause two distinct disorders
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Background
Inseparable tandem: evolution chooses ATP and Ca 2+ to control life, death and cellular signalling
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“…contexts, such as regulation and development of the immune, nervous, cardiovascular and musculoskeletal systems, and be involved in apoptosis and necrosis (Aramburu et al., 2004;Aramburu et al., 2000;Clipstone and Crabtree, 1992;Hemenway and Heitman, 1999;Hogan and Li, 2005;Rusnak and Mertz, 2000).”
Background
Updates in the treatment of ocular allergies
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Calcineurin in development and disease
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“CaN signaling is required for a broad spectrum of developmental processes in a variety of organ systems, including immune, kidney, heart, nervous, and musculoskeletal systems, as well as the differentiation of bone, cartilage, muscle, skin, and fat.(9,10,34,54) Therefore, inhibition of genes associated with CaN pathwa…”
Background
Global distribution of treatment resistance gene markers for leishmaniasis
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“…cell pathways has been reported by Kullas et al. (2007) who showed that the Ca2+-dependent calmodulin pathway, which uses calcium as internal mediator of stress response via activation of calcineurin (Aramburu et al. 2004), is also important for growth of Candida albicans in acidic environments.”
Background
Response of transcription factor NFATc3 to excitotoxic and traumatic brain insults: Identification of a subpopulation of reactive astrocytes
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Myb proteins regulate the expression of diverse target genes
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Transcriptional regulation of T cell tolerance
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“The calcineurin pathway is highly conserved in eukaryotic organisms (Aramburu et al., 2004).”
The Role of the Regulatory Subunit of Fission Yeast Calcineurin for in Vivo Activity and Its Relevance to FK506 Sensitivity
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“these two organisms [5].”
Self-citation
NFAT regulates calcium-sensing receptor-mediated TNF production
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“Regulation of NFAT5 by a calcineurin-dependent mechanism appears to be stimulus dependent and indirect as this isoform lacks the conserved regulatory domains that permit direct association with calcineurin, but may be induced in a calcineurin-dependent manner (1, 37, 57).”
Roles of Cch1 and Mid1 in Morphogenesis, Oxidative Stress Response and Virulence in Candida albicans
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Interplay between calcineurin and the Slt2 MAP-kinase in mediating cell wall integrity, conidiation and virulence in the insect fungal pathogen Beauveria bassiana
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Role of podocytes in lupus nephritis
Trivedi, S., Zeier, M., & Reiser, J. (2009) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfp427 · Cited by 35
A comparative transcriptomic study of vitamin E and an algae-based antioxidant as antioxidative agents: Investigation of replacing vitamin E with the algae-based antioxidant in broiler diets
Xiao, R., Power, R. F., Mallonee, D. H., Crowdus, C. A., Brennan, K. M., Ao, T., Pierce, J. L., & Dawson, K. A. (2010) · Poultry Science · doi:10.3382/ps.2010-01018 · Cited by 34
“…https://academic.oup.com/ps/article-abstract/90/1/136/1512655 by guest on 30 July 2018 mune responses and muscle development (Camps et al., 2000; Aramburu et al., 2004; Wang et al., 2008), whereas calpastatin, a gene that encodes a protease inhibitor and that was increased by E50 and EcoE on…”
Background
hERG1/Kv11.1 activation stimulates transcription of p21waf/cip in breast cancer cells via a calcineurin-dependent mechanism
Perez‐Neut, M., Rao, V. R., & Gentile, S. (2015) · Oncotarget · doi:10.18632/oncotarget.3797 · Cited by 34
“Calcineurin (CN) is a ubiquitously expressed serine/ threonine phosphatase that plays a fundamental role in many physiological or pathological states [22-24].”
Background
Down Syndrome Critical Region-1 Is a Transcriptional Target of Nuclear Factor of Activated T Cells-c1 within the Endocardium during Heart Development
Wu, H., Kao, S.-C., Barrientos, T., Baldwin, S. H., Olson, E. N., Crabtree, G. R., Zhou, B., & Chang, C.-P. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m703622200 · Cited by 34
Self-citation
Dissecting the Roles of the Calcineurin Pathway in Unisexual Reproduction, Stress Responses, and Virulence in Cryptococcus deneoformans
Fu, C., Donadio, N., Cardenas, M. E., & Heitman, J. (2017) · Genetics · doi:10.1534/genetics.117.300422 · Cited by 33
“…unisexual reproduction; stress response; virulence CALCINEURIN, the Ca2+/calmodulin-dependent proteinphosphatase, is conserved from fungi to humans, and it plays central functions in governing key cellular processes (Cyert et al. 1991; Liu et al. 1991b; Sugiura et al. 2002; Aramburu et al. 2004).”
BackgroundSelf-citation
Structural basis of calcineurin activation by calmodulin
Ye, Q., Feng, Y.-D., Yin, Y., Faucher, F., Currie, M. A., Rahman, M. N., Jin, J., Li, S., Wei, Q., & Jia, Z. (2013) · Cellular Signalling · doi:10.1016/j.cellsig.2013.08.033 · Cited by 33
Transcriptome Comparison Reveals the Adaptive Evolution of Two Contrasting Ecotypes of Zn/Cd Hyperaccumulator Sedum alfredii Hance
Yang, Q., Shohag, M. J. I., Feng, Y., He, Z. L., & Yang, X. (2017) · Frontiers in Plant Science · doi:10.3389/fpls.2017.00425 · Cited by 29
“Calmodulin senses the intracellular Ca2+ concentration and regulates a highly conserved type 2B protein phosphatase, calcineurin, which is vital for mediating cellular stress responses (Aramburu et al., 2004).”
Specific calcineurin targeting in macrophages confers resistance to inflammation via MKP‐1 and p38
Escolano, A., Martı́nez-Martı́nez, S., Alfranca, A., Urso, K., Izquierdo, H. M., Delgado, M., Martı́n, F., Sabio, G., Sancho, D., Arco, P. G., et al. (2014) · The EMBO Journal · doi:10.1002/embj.201386369 · Cited by 31
“Many CN-dependent processes described in mammals involve the regulation of the nuclear factor of activated T cells (NFAT) family of transcription factors (Crabtree & Olson, 2002; Hogan et al, 2003; Aramburu et al, 2004).”
Epigenetic regulation of RCAN1 expression in kidney disease and its role in podocyte injury
Li, H., Zhang, W., Zhong, F., Das, G. C., Xie, Y., Li, Z., Cai, W., Jiang, G., Choi, J. W., Sidani, M. A., et al. (2018) · Kidney International · doi:10.1016/j.kint.2018.07.023 · Cited by 32
Protein Phosphatase 3 Differentially Modulates Vascular Endothelial Growth Factor- and Fibroblast Growth Factor 2-Stimulated Cell Proliferation and Signaling in Ovine Fetoplacental Artery Endothelial Cells1
Wang, K., Song, Y., Chen, D., & Zheng, J. J. (2008) · Biology of Reproduction · doi:10.1095/biolreprod.108.068957 · Cited by 29
Immunosuppressants Affect Human Neural Stem Cells In Vitro but Not in an In Vivo Model of Spinal Cord Injury
Sontag, C. J., Nguyen, H. X., Kamei, N., Uchida, N., Anderson, A. J., & Cummings, B. J. (2013) · Stem Cells Translational Medicine · doi:10.5966/sctm.2012-0175 · Cited by 29
Protein Phosphatase 2B (PP2B, Calcineurin) in Paramecium: Partial Characterization Reveals That Two Members of the Unusually Large Catalytic Subunit Family Have Distinct Roles in Calcium-Dependent Processes
Fraga, D., Sehring, I. M., Kissmehl, R., Reiss, M., Gaines, R., Hinrichsen, R. D., & Plattner, H. (2010) · Eukaryotic Cell · doi:10.1128/ec.00322-09 · Cited by 27
“CaN participates in a variety of cellular signaling events and activation processes (3, 98).”
Background
Specific disruption of calcineurin-signaling in the distal convoluted tubule impacts the transcriptome and proteome, and causes hypomagnesemia and metabolic acidosis
Banki, E., Fisi, V., Moser, S. C., Wengi, A., Carrel, M., Loffing‐Cueni, D., Pentón, D., Kratschmar, D. V., Rizzo, L., Lienkamp, S. S., et al. (2021) · Kidney International · doi:10.1016/j.kint.2021.06.030 · Cited by 26
A Cytoplasmic New Catalytic Subunit of Calcineurin in Trypanosoma cruzi and Its Molecular and Functional Characterization
Orrego, P. R., Olivares, H., Cordero, E. M., Bressan, A., Cortéz, M., Sagua, H., Neira, I., González, J., da Silveira, J. F., Yoshida, N., et al. (2014) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0002676 · Cited by 27
“Calcineurin contributes in a variety of cellular signaling events and activation processes [45].”
Background
Signal Transduction Cascades Regulating Differentiation and Virulence in Botrytis cinerea
Schumacher, J. (2015) · Springer eBooks · doi:10.1007/978-3-319-23371-0_13 · Cited by 26
Calcineurin is an important factor involved in glucose uptake in human adipocytes
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“Calcineurin is a serine/threonine phosphatase controlled by cellular calcium concentrations [3].”
The Vertebrate RCAN Gene Family: Novel Insights into Evolution, Structure and Regulation
Serrano‐Candelas, E., Farré, D., Aranguren‐Ibáñez, Á., Martínez-Høyer, S., & Pérez‐Riba, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0085539 · Cited by 26
“Cn-NFATc signalling pathway is a crucial regulator of several biological processes such as: lymphocyte activation, angiogenesis, morphogenesis of the heart valves and neural and muscle development (reviewed in [11]).”
Calcineurin mediates acetylcholinesterase expression during calcium ionophore A23187-induced HeLa cell apoptosis
Zhu, H., Gao, W., Jiang, H. L., Wu, J., Shi, Y., & Zhang, X. (2007) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2007.01.008 · Cited by 25
“The calcineurin/NFAT signaling pathway has recently been implicated in development and function of the nervous system, the cardiovascular system, the musculoskeletal development, and in cardiac growth and function [31,48].”
Calcineurin and Calcium Channel CchA Coordinate the Salt Stress Response by Regulating Cytoplasmic Ca 2+ Homeostasis in Aspergillus nidulans
Wang, S., Liu, X., Qian, H., Zhang, S., & Lü, L. (2016) · Applied and Environmental Microbiology · doi:10.1128/aem.00330-16 · Cited by 23
Deficiency of Cardiac Natriuretic Peptide Signaling Promotes Peripartum Cardiomyopathy-Like Remodeling in the Mouse Heart
Otani, K., Tokudome, T., Kamiya, C., Mao, Y., Nishimura, H., Hasegawa, T., Arai, Y., Kaneko, M., Shioi, G., Ishida, J., et al. (2019) · Circulation · doi:10.1161/circulationaha.119.039761 · Cited by 23
Stimulating Fungi Pleurotus ostreatus with Hydrocortisone
Dehshibi, M. M., Chiolerio, A., Nikolaidou, A. E., Mayne, R., Gandía, A., Ashtari-Majlan, M., & Adamatzky, A. (2021) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.1c00752 · Cited by 21
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Kozubowski, L., Thompson, J. W., Cardenas, M. E., Moseley, M. A., & Heitman, J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025280 · Cited by 26
“Calcineurin is a calcium-calmodulin-activated protein phosphatase consisting of two subunits: a 60 kDa catalytic A subunit and a 19 kDa regulatory B subunit, both of which are essential for enzyme activity [1,2].”
BackgroundSelf-citation
An Antiproliferative Genetic Screening Identifies a Peptide Aptamer That Targets Calcineurin and Up-regulates Its Activity
de Chassey, B., Mikaélian, I., Mathieu, A., Bickle, M., Olivier, D., Négre, D., Cosset, F., Rudkin, B. B., & Colas, P. (2006) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m600102-mcp200 · Cited by 22
“In contrast, calcineurin (of which CNA is the catalytic subunit) is a well-studied protein phosphatase that plays a key role in coupling Ca signaling to cellular responses (reviewed in (23)).”
Background
Inhibition of calcineurin/NFAT pathway plays an essential role in renoprotective effect of tropisetron in early stage of diabetic nephropathy
Barzegar‐Fallah, A., Alimoradi, H., Razmi, A., Dehpour, A. R., Asgari, M., & Shafiei, M. (2015) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2015.10.019 · Cited by 21
Effect of cyclosporin A on proteinuria in the course of glomerulopathy associated with WT1 mutations
Wasilewska, A. M., Kuroczycka–Saniutycz, E., & Zoch-Zwierz, W. M. (2010) · European Journal of Pediatrics · doi:10.1007/s00431-010-1278-4 · Cited by 20
“Calcineurin is a ubiquitously expressed serine/threonine phosphatase [1].”
Background
Downregulation of Calcineurin Gene Is Associated with Glucantime(®) Resiatance in Leishmania infantum.
Erfan, M. B. K., Mohebali, M., Kazemirad, E., Hajjaran, H., Edrissian, G., Mamishi, S., Saffari, M., Raoofian, R., & Heidari, M. (2013) · Europe PMC (PubMed Central) · Cited by 20
Effects of Ultraviolet A‐1 Radiation on Calcineurin Activity and Cytokine Production in (Skin) Cell Cultures†
Smit, N. P. M., Musson, R. E. A., Romijn, F. P. H. T. M., van Rossum, H. H., & PELT, J. V. (2009) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.2009.00650.x · Cited by 20
“In keratinocytes, for instance, Cn plays a role in cell signaling and differentiation (4,5).”
Background
Calcineurin Activity and Inhibition in Skin and (Epi)Dermal Cell Cultures
Smit, N. P. M., van Rossum, H. H., Romijn, F. P. H. T. M., Sellar, K. J., Breetveld, M., Gibbs, S., & PELT, J. V. (2008) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5701244 · Cited by 19
“In T cells, it is responsible for the dephosphorylation of the NFAT (nuclear factor of activated T cells), and its subsequent nuclear translocation ultimately results in T-cell activation (”
Background
Chapter 5 Pharmacology of Ciliated Protozoa—Drug (In)Sensitivity and Experimental Drug (Ab)Use
Plattner, H., Sehring, I. M., Schilde, C., & Ladenburger, E. (2009) · International review of cytology · doi:10.1016/s1937-6448(08)01805-4 · Cited by 19
“This would be even more important as calcineurin governs a variety of cellular functions (Aramburu et al., 2004), probably also in Paramecium where it is localized to distinct sites (Momayezi et al.”
Background
Cyclooxygenase-2 induction requires activation of nuclear factor of activated T-cells in Beas-2B cells after vanadium exposure and plays an anti-apoptotic role
Tang, H., Sun, Y. N., Xiu, Q., Lu, H. Y., & Han, H.-X. (2007) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2007.09.016 · Cited by 18
The C2 Domain Protein Cts1 Functions in the Calcineurin Signaling Circuit during High-Temperature Stress Responses in Cryptococcus neoformans
Aboobakar, E. F., Wang, X., Heitman, J., & Kozubowski, L. (2011) · Eukaryotic Cell · doi:10.1128/ec.05148-11 · Cited by 17
“neoformans growth at 37°C and for its virulence (1, 21, 35).”
BackgroundSelf-citation
Had1 Is Required for Cell Wall Integrity and Fungal Virulence in Cryptococcus neoformans
Jung, W. H., Son, Y.-E., Oh, S., Fu, C., Kim, H., Kwak, J., Cardenas, M. E., Heitman, J., & Park, H.-S. (2017) · G3 Genes Genomes Genetics · doi:10.1534/g3.117.300444 · Cited by 17
“DISCUSSION Given that calcineurin is a key pathway regulating stress responses, mating, and fungal virulence, identification and characterization of calcineurin targets is crucial for understanding the calcineurin signaling network (Aramburu et al. 2004; Steinbach et al. 2006; Goldman et al. 2014).”
BackgroundInfluentialSelf-citation
Tetrandrine alleviates podocyte injury via calcium-dependent calpain-1 signaling blockade
Ding, Y., Tang, X., Wang, Y., Yu, D., Zhu, C., & Yu, J. (2021) · BMC Complementary Medicine and Therapies · doi:10.1186/s12906-021-03469-x · Cited by 16
“Calcineurin is clinically important as a direct target of the immunosuppressive drug CsA [17, 29].”
Background
Emerging Targets of the GnRH Receptor: Novel Interactions with Wnt Signalling Mediators
Gardner, S., & Pawson, A. J. (2008) · Neuroendocrinology · doi:10.1159/000165377 · Cited by 17
“…(CaN) is also Ca 2+ - dependent through activation by CaM, and is a Ser- and Thr-protein phosphatase with many potential substrates including nuclear factor of activated T cells (NFAT), which is a transcription factor directly regulated by Ca 2+ [Aramburu et al., 2004] (see ‘Future Perspectives’).”
Background
FK506 inhibits the mice glomerular mesangial cells proliferation by affecting the transforming growth factor-βand Smads signal pathways
Ren, Q., Li, W., & Yu, S. (2014) · Renal Failure · doi:10.3109/0886022x.2014.882713 · Cited by 15
“FK506 is a new generation of CNI used in the treatment of kidney diseases and graft rejection by inhibiting the activation of T cells, the proliferation of dependent B cells on Th helper cells, and the expression of lymphokines such as IL-2, IL-3, and g-interferon, and IL-2R, to reduce immune inhibitory effects.(17) O…”
Background
Calcineurin regulates phosphorylation status of transcription factor osterix
Okamura, H., Amorim, B. R., Wang, J., Yoshida, K., & Haneji, T. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.12.094 · Cited by 15
From phagocytosis to metaforosis: Calcineurin’s deadly role in innate processing of fungi
Armstrong-James, D. P. H., de Boer, L. L., Bercusson, A., & Shah, A. (2018) · PLoS Pathogens · doi:10.1371/journal.ppat.1006627 · Cited by 13
Calcineurin Plays an Important Role in the Shell Formation of Pearl Oyster (Pinctada fucata)
Li, C., Hu, Y., Liang, J., Kong, Y., Huang, J. L., Feng, Q., Li, S., Zhang, G., Xie, L., & Zhang, R. (2009) · Marine Biotechnology · doi:10.1007/s10126-009-9204-3 · Cited by 13
“It is well known that CN is involved in the bone metabolism and chondrogenesis in mammalian through CN/NFAT signal pathway (Aramburu et al. 2000; Aramburu et al. 2004 ).”
Background
Cellular and Molecular Consequences of Calcineurin Aα Gene Deletion
Sun, L., Zhu, L.-L., Zaidi, N., Yang, G., Moonga, B. S., Abe, E., Iqbal, J. Z., Epstein, S., Blair, H. C., Huang, C. L.-H., et al. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1402.050 · Cited by 13

Authors: Aramburu, J., Heitman, J., & Crabtree, G. R.
Affiliations: Howard Hughes Medical Institute (US)
ORCID: Heitman, Joseph
Crabtree, Gerald R.
Venue: The EMBO Reports
Publisher: Springer Science and Business Media LLC
Published: 2004-04-01
Volume: 5
Issue: 4
Pages: 343-348
ISSN: 1469-221X (ISSN-L)
1469-3178
DOI: 10.1038/sj.embor.7400133
PMC: PMC1299038
OpenAlex: W1967336595
Cited by: 156
References: 18
Citations by year: 2026: 1 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 1 · 2021: 13 · 2020: 1 · 2019: 3 · 2018: 7 · 2017: 4 · 2016: 6 · 2015: 13 · 2014: 9 · 2013: 9 · 2012: 8
FWCI: 3.44
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: EMBO Reports (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Calpain Protease Function and Regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
Keywords: calcineurin, calcium signaling, NFAT, calcineurin-NFAT pathway
MeSH terms: Animals, DNA-Binding Proteins, Eukaryotic Cells, Heart, Humans, Lymphocytes, Nervous System Physiological Phenomena, Nuclear Proteins, Transcription Factors, Signal Transduction, Neovascularization, Physiologic, Calcineurin, NFATC Transcription Factors

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Calcineurin: a central controller of signalling in eukaryotes: Workshop on the Calcium/Calcineurin/NFAT Pathway: Regulation and Function

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