{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Calmodulin‐binding transcription activator 2 (CAMTA2) is a multifunctional, calcium‐responsive transcription regulator that mediates distinct gene expression programs in diverse biological systems. In the cardiovascular system, CAMTA2 acts as an indispensable coactivator for cardiac hypertrophy by interacting with the homeodomain protein Nkx2‐5 to activate the transcription of hypertrophy‐associated genes (e.g., atrial natriuretic factor). Genetic polymorphisms that enhance CAMTA2’s transcriptional activity have been linked to an increased risk of left ventricular hypertrophy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the nervous system, a hypomorphic mutation located in the 5′‐untranslated region of a CAMTA2 isoform leads to a post‐transcriptional inhibition of its protein expression and is associated with a syndromic phenotype featuring tremulous dystonia, spasticity, and white matter disease—demonstrating its vital role in neural development and homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In plants, CAMTA2 functions as a Ca²⁺‐dependent activator of stress‐responsive genes. Notably, it promotes the expression of ALUMINUM‐ACTIVATED MALATE TRANSPORTER1 (ALMT1), thereby facilitating malate exudation from roots and contributing to aluminum tolerance. This activation is part of a signaling cascade involving calmodulin and other Ca²⁺ sensors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In oncology, particularly in colon cancer, CAMTA2 is frequently overexpressed and its elevated levels correlate with poor patient survival. Functional studies indicate that CAMTA2 promotes cell proliferation and migration by, in part, augmenting Wnt/β-catenin signaling. Its expression is modulated post-transcriptionally by miR-28-5p, underscoring its role in tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Additional studies have identified significant changes in CAMTA2 expression in ovarian follicular atresia, suggesting that it may serve as a marker for cell fate decisions in reproductive tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, emerging evidence points to a regulatory mechanism in which CAMTA2 protein stability is controlled by MAP kinase–dependent phosphorylation events that create phosphodegron motifs targeted by the ubiquitin ligase FBXW7, thus linking CAMTA2 turnover to broader cellular signaling networks."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies establish CAMTA2 as a versatile mediator of Ca²⁺-dependent transcriptional responses that govern cardiac growth, neural function, stress adaptation in plants, and cancer progression.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Robert J Schwartz, Michael D Schneider "}, {"type": "b", "children": [{"type": "t", "text": "CAMTA in cardiac hypertrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2006.04.015"}], "href": "https://doi.org/10.1016/j.cell.2006.04.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16678087"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16678087"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Wei-Hua Song, Ya-Hui Lin, Kai Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A functional variant in the coding region of CAMTA2 is associated with left ventricular hypertrophy by affecting the activation of Nkx2.5-dependent transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hypertens (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/HJH.0000000000000873"}], "href": "https://doi.org/10.1097/HJH.0000000000000873"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26886562"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26886562"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Dorota Monies, Hussam Abou Al-Shaar, Ewa A Goljan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a novel genetic locus underlying tremor and dystonia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genomics (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s40246-017-0123-5"}], "href": "https://doi.org/10.1186/s40246-017-0123-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29110692"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29110692"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Liujie Wu, Ayan Sadhukhan, Yuriko Kobayashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of phosphatidylinositol metabolism in aluminum-induced malate secretion in Arabidopsis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Bot (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jxb/erz179"}], "href": "https://doi.org/10.1093/jxb/erz179"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30977815"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30977815"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xue Zhu, Peng Wang, Zhimin Bai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Calmodulin-like protein CML24 interacts with CAMTA2 and WRKY46 to regulate ALMT1-dependent Al resistance in Arabidopsis thaliana."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "New Phytol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/nph.17812"}], "href": "https://doi.org/10.1111/nph.17812"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34665465"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34665465"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Xiao-Feng Luan, Lei Wang, Xue-Feng Gai "}, {"type": "b", "children": [{"type": "t", "text": "The miR-28-5p-CAMTA2 axis regulates colon cancer progression via Wnt/β-catenin signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.29536"}], "href": "https://doi.org/10.1002/jcb.29536"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31709644"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31709644"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Elena Terenina, Stephane Fabre, Agnès Bonnet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differentially expressed genes and gene networks involved in pig ovarian follicular atresia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Physiol Genomics (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/physiolgenomics.00069.2016"}], "href": "https://doi.org/10.1152/physiolgenomics.00069.2016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27940565"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27940565"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Neha Singh, András Zeke, Attila Reményi "}, {"type": "b", "children": [{"type": "t", "text": "Systematic Discovery of FBXW7-Binding Phosphodegrons Highlights Mitogen-Activated Protein Kinases as Important Regulators of Intracellular Protein Levels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms23063320"}], "href": "https://doi.org/10.3390/ijms23063320"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35328741"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35328741"}]}]}]}