{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTescalcin (TESC), also known as CHP3, is an EF‐hand Ca²⁺‐binding protein that plays a key role in normal cellular homeostasis. Biochemically, TESC directly binds to a proximal juxtamembrane region of the Na⁺/H⁺ exchanger NHE1, facilitating its biosynthetic maturation, membrane targeting, and stabilization, thereby promoting optimal ion transport activity. Its function relies on both Ca²⁺ binding and N‐myristoylation domains, and high affinity, exothermic interactions have been demonstrated between TESC and its targets. In addition, TESC expression is tightly regulated during cellular differentiation—for example, in hematopoietic cells where it is upregulated during granulocytic lineage commitment, as well as in cardiac cells where TESC modulates hypertrophic signaling via effects on kinases such as GSK3. These cellular roles are further supported by its interaction with regulatory proteins such as the COP9 signalosome subunit CSN4."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAberrant TESC expression has been implicated in the initiation and progression of several malignancies. Elevated levels of TESC have been observed in colorectal, non‐small cell lung, gastric, hepatocellular, esophageal, and renal cancers, where it promotes tumor cell invasion, metastasis, and the epithelial–mesenchymal transition (EMT). In these contexts, TESC augments oncogenic signaling pathways—including the IGF1R/c‐Src/STAT3 and Akt/NF‑κB cascades—to enhance cancer stem cell properties, increase resistance to therapy, and support tumor growth in vivo. In parallel, genetic and epigenetic alterations affecting TESC (for example, the rs7294919 variant) have been associated with region‐specific changes in hippocampal morphology, suggesting roles in neurodevelopment and potential links to neuropsychiatric conditions. Collectively, these observations underscore the diverse and multifaceted functions of TESC in both normal physiology and disease, highlighting its potential as a diagnostic marker and therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "17"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hans C Zaun, Alvin Shrier, John Orlowski "}, {"type": "b", "children": [{"type": "t", "text": "Calcineurin B homologous protein 3 promotes the biosynthetic maturation, cell surface stability, and optimal transport of the Na+/H+ exchanger NHE1 isoform."}]}, {"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.M800267200"}], "href": "https://doi.org/10.1074/jbc.M800267200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18321853"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18321853"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Konstantin Levay, Vladlen Z Slepak "}, {"type": "b", "children": [{"type": "t", "text": "Up- or downregulation of tescalcin in HL-60 cells is associated with their differentiation to either granulocytic or macrophage-like lineage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2010.01.007"}], "href": "https://doi.org/10.1016/j.yexcr.2010.01.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20060826"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20060826"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hans C Zaun, Alvin Shrier, John Orlowski "}, {"type": "b", "children": [{"type": "t", "text": "N-myristoylation and Ca2+ binding of calcineurin B homologous protein CHP3 are required to enhance Na+/H+ exchanger NHE1 half-life and activity at the plasma membrane."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.394700"}], "href": "https://doi.org/10.1074/jbc.M112.394700"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22984264"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22984264"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Konstantin Levay, Vladlen Z Slepak "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of Cop9 signalosome activity by the EF-hand Ca2+-binding protein tescalcin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.139592"}], "href": "https://doi.org/10.1242/jcs.139592"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24659803"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24659803"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Soushi Kobayashi, Tomoe Y Nakamura, Shigeo Wakabayashi "}, {"type": "b", "children": [{"type": "t", "text": "Calcineurin B homologous protein 3 negatively regulates cardiomyocyte hypertrophy via inhibition of glycogen synthase kinase 3 phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Cell Cardiol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yjmcc.2015.04.018"}], "href": "https://doi.org/10.1016/j.yjmcc.2015.04.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25935310"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25935310"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Simon Fuchs, Sierra C Hansen, Marie Markones, et al. 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