{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRCAN1—also known as DSCR1 or calcipressin 1—is a critical gene on human chromosome 21 whose dosage increase in Down syndrome underlies a diverse range of cellular effects. RCAN1 functions primarily as an endogenous inhibitor of calcineurin, the Ca²⁺/calmodulin‐dependent phosphatase that dephosphorylates and activates NFAT transcription factors. Its various isoforms (e.g. RCAN1‐1 and RCAN1‐4) are dynamically regulated by extracellular signals such as vascular endothelial growth factor, thrombin, and calcium fluxes. In addition, RCAN1 activity is fine‐tuned by post‐translational modifications—including phosphorylation (often mediated by kinases such as Dyrk1A and NIK) and regulated degradation via the ubiquitin–proteasome and chaperone‐mediated autophagy pathways—which together determine its inhibitory action on calcineurin–NFAT signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn neuronal systems, aberrant RCAN1 expression has been implicated in neurodegenerative disorders. For example, oxidative stress and amyloid‐β toxicity upregulate RCAN1 in the brains of individuals with Alzheimer’s disease, a process that—by inhibiting calcineurin—leads to decreased tau dephosphorylation and facilitates tau hyperphosphorylation via increased GSK3β activity. Similarly, studies in Huntington disease suggest that reduced RCAN1 levels may compromise protective phosphorylation events, whereas sustained overexpression eventually contributes to caspase activation, mitochondrial dysfunction, and neuronal apoptosis. Notably, the cellular consequences of RCAN1 induction are context‐dependent; transient upregulation may afford neuroprotection, yet chronic elevation drives pathological changes that can be mitigated by antioxidants such as lycopene."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "18", "end_ref": "27"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond the nervous system, RCAN1 plays multifaceted roles in vascular and tumor biology. In endothelial cells, it regulates key aspects of angiogenesis by modulating VEGF receptor internalization, cell polarity, adhesion, and migration, thereby contributing to the formation of neovessels as well as serving as a brake on excessive vascular growth. In various cancer models—including endometrial, hepatocellular, and oral squamous cell carcinomas—RCAN1 expression is counteracted by specific microRNAs and long non‐coding RNAs; this loss of RCAN1 can enhance cell proliferation, motility, and metastatic potential. Additional functions such as the regulation of vesicle exocytosis and the promotion of mitophagy under hypoxic conditions further underscore RCAN1’s involvement in maintaining cellular homeostasis and point to its potential as a therapeutic target in oncologic and vascular disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "28", "end_ref": "39"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "J J Fuentes, L Genescà, T J Kingsbury, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DSCR1, overexpressed in Down syndrome, is an inhibitor of calcineurin-mediated signaling pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2000)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/9.11.1681"}], "href": "https://doi.org/10.1093/hmg/9.11.1681"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "10861295"}], "href": "https://pubmed.ncbi.nlm.nih.gov/10861295"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sandra Cristina Pfister, Gláucia Maria Machado-Santelli, Sang Won Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutational analyses of the signals involved in the subcellular location of DSCR1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cell Biol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2121-3-24"}], "href": "https://doi.org/10.1186/1471-2121-3-24"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12225619"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12225619"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Lali Genescà, Anna Aubareda, Juan J Fuentes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphorylation of calcipressin 1 increases its ability to inhibit calcineurin and decreases calcipressin half-life."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20030267"}], "href": "https://doi.org/10.1042/BJ20030267"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12809556"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12809556"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Boris A Hesser, Xiao Huan Liang, Gieri Camenisch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Down syndrome critical region protein 1 (DSCR1), a novel VEGF target gene that regulates expression of inflammatory markers on activated endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2004-01-0273"}], "href": "https://doi.org/10.1182/blood-2004-01-0273"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15016650"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15016650"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yong-Gang Yao, Elia J Duh "}, {"type": "b", "children": [{"type": "t", "text": "VEGF selectively induces Down syndrome critical region 1 gene expression in endothelial cells: a mechanism for feedback regulation of angiogenesis?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2004.06.176"}], "href": "https://doi.org/10.1016/j.bbrc.2004.06.176"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15358155"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15358155"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Takashi Minami, Keiko Horiuchi, Mai Miura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Vascular endothelial growth factor- and thrombin-induced termination factor, Down syndrome critical region-1, attenuates endothelial cell proliferation and angiogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M406454200"}], "href": "https://doi.org/10.1074/jbc.M406454200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15448146"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15448146"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "C D Harris, G Ermak, K J A Davies "}, {"type": "b", "children": [{"type": "t", "text": "Multiple roles of the DSCR1 (Adapt78 or RCAN1) gene and its protein product calcipressin 1 (or RCAN1) in disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Life Sci (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00018-005-5085-4"}], "href": "https://doi.org/10.1007/s00018-005-5085-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16231093"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16231093"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Damien J Keating, Chen Chen, Melanie A Pritchard "}, {"type": "b", "children": [{"type": "t", "text": "Alzheimer's disease and endocytic dysfunction: clues from the Down syndrome-related proteins, DSCR1 and ITSN1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ageing Res Rev (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.arr.2005.11.001"}], "href": "https://doi.org/10.1016/j.arr.2005.11.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16442855"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16442855"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Takashi Minami, Mai Miura, William C Aird, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Thrombin-induced autoinhibitory factor, Down syndrome critical region-1, attenuates NFAT-dependent vascular cell adhesion molecule-1 expression and inflammation in the endothelium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M513112200"}], "href": "https://doi.org/10.1074/jbc.M513112200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16627481"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16627481"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Young Sun Kim, Kyung-Ok Cho, Hong Joon Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Down syndrome candidate region 1 increases the stability of the IkappaBalpha protein: implications for its anti-inflammatory effects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M604659200"}], "href": "https://doi.org/10.1074/jbc.M604659200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17062574"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17062574"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Liuliang Qin, Dezheng Zhao, Xin Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Down syndrome candidate region 1 isoform 1 mediates angiogenesis through the calcineurin-NFAT pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-06-0126"}], "href": "https://doi.org/10.1158/1541-7786.MCR-06-0126"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17114339"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17114339"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Craig R Bush, Jennifer M Havens, Brian M Necela, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional genomic analysis reveals cross-talk between peroxisome proliferator-activated receptor gamma and calcium signaling in human colorectal cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M702708200"}], "href": "https://doi.org/10.1074/jbc.M702708200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17565986"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17565986"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Hai Wu, Shih-chu Kao, Tomasa Barrientos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Down syndrome critical region-1 is a transcriptional target of nuclear factor of activated T cells-c1 within the endocardium during heart development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M703622200"}], "href": "https://doi.org/10.1074/jbc.M703622200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17693409"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17693409"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Amber N Mitchell, Lalithapriya Jayakumar, Issam Koleilat, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Brain expression of the calcineurin inhibitor RCAN1 (Adapt78)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Biochem Biophys (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.abb.2007.08.030"}], "href": "https://doi.org/10.1016/j.abb.2007.08.030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17910944"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17910944"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Eun Jung Lee, Su Ryeon Seo, Ji Won Um, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NF-kappaB-inducing kinase phosphorylates and blocks the degradation of Down syndrome candidate region 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M706707200"}], "href": "https://doi.org/10.1074/jbc.M706707200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18056702"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18056702"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "D J Mahoney, A Safdar, G Parise, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gene expression profiling in human skeletal muscle during recovery from eccentric exercise."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Regul Integr Comp Physiol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpregu.00847.2007"}], "href": "https://doi.org/10.1152/ajpregu.00847.2007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18321953"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18321953"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Sara Martínez-Martínez, Lali Genescà, Antonio Rodríguez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The RCAN carboxyl end mediates calcineurin docking-dependent inhibition via a site that dictates binding to substrates and regulators."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0812544106"}], "href": "https://doi.org/10.1073/pnas.0812544106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19332797"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19332797"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Gennady Ermak, Karl J Hench, Kevin T Chang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulator of calcineurin (RCAN1-1L) is deficient in Huntington disease and protective against mutant huntingtin toxicity in vitro."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M900639200"}], "href": "https://doi.org/10.1074/jbc.M900639200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19270310"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19270310"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Heng Liu, Pin Wang, Weihong Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Degradation of regulator of calcineurin 1 (RCAN1) is mediated by both chaperone-mediated autophagy and ubiquitin proteasome pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.09-134296"}], "href": "https://doi.org/10.1096/fj.09-134296"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19509306"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19509306"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Xiulian Sun, Yili Wu, Bin Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulator of calcineurin 1 (RCAN1) facilitates neuronal apoptosis through caspase-3 activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.177519"}], "href": "https://doi.org/10.1074/jbc.M110.177519"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21216952"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21216952"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Gennady Ermak, Melanie A Pritchard, Sladjana Dronjak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Do RCAN1 proteins link chronic stress with neurodegeneration?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.11-185728"}], "href": "https://doi.org/10.1096/fj.11-185728"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21680892"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21680892"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Ana Lloret, Mari-Carmen Badia, Esther Giraldo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Amyloid-β toxicity and tau hyperphosphorylation are linked via RCAN1 in Alzheimer's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Alzheimers Dis (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3233/JAD-2011-110890"}], "href": "https://doi.org/10.3233/JAD-2011-110890"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21876249"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21876249"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Min-Su Jung, Jung-Hwa Park, Young Shin Ryu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of RCAN1 protein activity by Dyrk1A protein-mediated phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.253971"}], "href": "https://doi.org/10.1074/jbc.M111.253971"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21965663"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21965663"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Yili Wu, Weihong Song "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of RCAN1 translation and its role in oxidative stress-induced apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.12-213124"}], "href": "https://doi.org/10.1096/fj.12-213124"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23038757"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23038757"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Heshan Peiris, Daphne Dubach, Claire F Jessup, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RCAN1 regulates mitochondrial function and increases susceptibility to oxidative stress in mammalian cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oxid Med Cell Longev (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2014/520316"}], "href": "https://doi.org/10.1155/2014/520316"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25009690"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25009690"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Helen Wong, Josien Levenga, Peter Cain, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RCAN1 overexpression promotes age-dependent mitochondrial dysregulation related to neurodegeneration in Alzheimer's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Neuropathol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00401-015-1499-8"}], "href": "https://doi.org/10.1007/s00401-015-1499-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26497675"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26497675"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Seiyoung Lim, Sinwoo Hwang, Ji Hoon Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lycopene inhibits regulator of calcineurin 1-mediated apoptosis by reducing oxidative stress and down-regulating Nucling in neuronal cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Nutr Food Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mnfr.201600530"}], "href": "https://doi.org/10.1002/mnfr.201600530"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27928873"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27928873"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Allan V Espinosa, Motoo Shinohara, Leonardo M Porchia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulator of calcineurin 1 modulates cancer cell migration in vitro."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Exp Metastasis (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10585-009-9251-1"}], "href": "https://doi.org/10.1007/s10585-009-9251-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19306109"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19306109"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Kurt J Sales, David Maldonado-Pérez, Vivien Grant, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prostaglandin F(2alpha)-F-prostanoid receptor regulates CXCL8 expression in endometrial adenocarcinoma cells via the calcium-calcineurin-NFAT pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2009.09.018"}], "href": "https://doi.org/10.1016/j.bbamcr.2009.09.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19819266"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19819266"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Monica Y Lee, Sean M Garvey, Alex S Baras, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Integrative genomics identifies DSCR1 (RCAN1) as a novel NFAT-dependent mediator of phenotypic modulation in vascular smooth muscle cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddp511"}], "href": "https://doi.org/10.1093/hmg/ddp511"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19926569"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19926569"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Gloria W C Tam, Louie N van de Lagemaat, Richard Redon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Confirmed rare copy number variants implicate novel genes in schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Soc Trans (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BST0380445"}], "href": "https://doi.org/10.1042/BST0380445"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20298200"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20298200"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Sung-Young Shin, Hee Won Yang, Jeong-Rae Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A hidden incoherent switch regulates RCAN1 in the calcineurin-NFAT signaling network."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.076034"}], "href": "https://doi.org/10.1242/jcs.076034"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21172821"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21172821"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Lijun Sun, Yuewen Hao, Rui An, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of Rcan1-1L inhibits hypoxia-induced cell apoptosis through induction of mitophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cells (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.14348/molcells.2014.0103"}], "href": "https://doi.org/10.14348/molcells.2014.0103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25377251"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25377251"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Ahmad F Alghanem, Emma L Wilkinson, Maxine S Emmett, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RCAN1.4 regulates VEGFR-2 internalisation, cell polarity and migration in human microvascular endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Angiogenesis (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10456-017-9542-0"}], "href": "https://doi.org/10.1007/s10456-017-9542-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28271280"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28271280"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Chaojie Wang, Motoyasu Saji, Steven E Justiniano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RCAN1-4 is a thyroid cancer growth and metastasis suppressor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "JCI Insight (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/jci.insight.90651"}], "href": "https://doi.org/10.1172/jci.insight.90651"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28289712"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28289712"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Changlong Song, Dianqiu Li, Hongyu Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The competing endogenous circular RNA ADAMTS14 suppressed hepatocellular carcinoma progression through regulating microRNA-572/regulator of calcineurin 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.26764"}], "href": "https://doi.org/10.1002/jcp.26764"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30317540"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30317540"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Yan Yun, Yun Zhang, Chen Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulator of calcineurin 1 is a novel RNA-binding protein to regulate neuronal apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41380-019-0487-0"}], "href": "https://doi.org/10.1038/s41380-019-0487-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31451750"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31451750"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Dong Ha Kim, Sojung Park, HyeongRyul Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tumor-derived exosomal miR-619-5p promotes tumor angiogenesis and metastasis through the inhibition of RCAN1.4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2020.01.023"}], "href": "https://doi.org/10.1016/j.canlet.2020.01.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32004570"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32004570"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "G Zhang, Z Chen, Y Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of miR-103a-3p suppresses the proliferation in oral squamous cell carcinoma cells via targeting RCAN1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neoplasma (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4149/neo_2020_190430N382"}], "href": "https://doi.org/10.4149/neo_2020_190430N382"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32122140"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32122140"}]}]}]}