{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTJP2, also known as zonula occludens‐2 (ZO‐2), is a multidomain scaffolding protein central to the assembly and maintenance of tight junctions in epithelial cells. Through its conserved PDZ domains, TJP2 interacts with a wide array of adhesion receptors and signaling molecules, thereby not only organizing the membrane‐attached junctional complex but also linking cell–cell contact sites to the nucleus to regulate transcriptional programs and apoptosis. This dual role in both structural barrier formation and nuclear signaling makes TJP2 a critical regulator of cell polarity and homeostasis"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n \n<br><br>\nAlterations in TJP2 function, arising from truncating or missense mutations, have been linked to severe clinical phenotypes. In the liver, mutations in TJP2 disrupt tight junction structure and protein localization, impairing bile acid transport and resulting in cholestatic liver diseases such as progressive familial intrahepatic cholestasis type 4 (PFIC4); these mutations also correlate with a spectrum of pediatric and adult cholestatic phenotypes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "9"}]}, {"type": "t", "text": " Likewise, in the inner ear, dysregulation of TJP2—whether by overexpression or mutation—is associated with altered apoptotic signaling and compromised tight junction integrity, contributing to adult‐onset and non‐syndromic hearing impairment"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n \n<br><br>\nBeyond its role at the plasma membrane, TJP2 shuttles into the nucleus where it regulates the localization and function of key transcription factors such as YAP2 and TEAD, thereby influencing cell proliferation, survival, and potentially tumor suppression. By modulating nuclear import of these factors and thereby affecting pro‐apoptotic signals, TJP2 emerges as an important integrator of cell junction integrity and gene expression programs that may be harnessed in therapeutic strategies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Victoria E H Carlton, Baruch Z Harris, Erik G Puffenberger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Complex inheritance of familial hypercholanemia with associated mutations in TJP2 and BAAT."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng1147"}], "href": "https://doi.org/10.1038/ng1147"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12704386"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12704386"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Tsutomu Oka, Eline Remue, Kris Meerschaert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional complexes between YAP2 and ZO-2 are PDZ domain-dependent, and regulate YAP2 nuclear localization and signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20100870"}], "href": "https://doi.org/10.1042/BJ20100870"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20868367"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20868367"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Lorenza González-Mariscal, Jael Miranda, Arturo Raya-Sandino, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZO-2, a tight junction protein involved in gene expression, proliferation, apoptosis, and cell size regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann N Y Acad Sci (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/nyas.13334"}], "href": "https://doi.org/10.1111/nyas.13334"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28415133"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28415133"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Tom Walsh, Sarah B Pierce, Danielle R Lenz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genomic duplication and overexpression of TJP2/ZO-2 leads to altered expression of apoptosis genes in progressive nonsyndromic hearing loss DFNA51."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2010.05.011"}], "href": "https://doi.org/10.1016/j.ajhg.2010.05.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20602916"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20602916"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Melissa Sambrotta, Sandra Strautnieks, Efterpi Papouli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in TJP2 cause progressive cholestatic liver disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.2918"}], "href": "https://doi.org/10.1038/ng.2918"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24614073"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24614073"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Hong-Yang Wang, Ya-Li Zhao, Qiong Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of Two Disease-causing Genes TJP2 and GJB2 in a Chinese Family with Unconditional Autosomal Dominant Nonsyndromic Hereditary Hearing Impairment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Chin Med J (Engl) (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4103/0366-6999.171440"}], "href": "https://doi.org/10.4103/0366-6999.171440"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26668150"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26668150"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "María Tello-Lafoz, Gonzalo Martínez-Martínez, Cristina Rodríguez-Rodríguez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sorting nexin 27 interactome in T-lymphocytes identifies zona occludens-2 dynamic redistribution at the immune synapse."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Traffic (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/tra.12492"}], "href": "https://doi.org/10.1111/tra.12492"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28477369"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28477369"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Giovanni Vitale, Stefano Gitto, Francesco Raimondi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cryptogenic cholestasis in young and adults: ATP8B1, ABCB11, ABCB4, and TJP2 gene variants analysis by high-throughput sequencing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Gastroenterol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00535-017-1423-1"}], "href": "https://doi.org/10.1007/s00535-017-1423-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29238877"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29238877"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Chun-Shan Wei, Naja Becher, Jenny Blechingberg Friis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "New tight junction protein 2 variant causing progressive familial intrahepatic cholestasis type 4 in adults: A case report."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "World J Gastroenterol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3748/wjg.v26.i5.550"}], "href": "https://doi.org/10.3748/wjg.v26.i5.550"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32089630"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32089630"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Helios Gallego-Gutiérrez, Laura González-González, Leticia Ramírez-Martínez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tight junction protein ZO-2 modulates the nuclear accumulation of transcription factor TEAD."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E20-07-0470"}], "href": "https://doi.org/10.1091/mbc.E20-07-0470"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34010016"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34010016"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Hanyue Ouyang, Shuang Wu, Wangji Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "p120 RasGAP and ZO-2 are essential for Hippo signaling and tumor-suppressor function mediated by p190A RhoGAP."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2023.113486"}], "href": "https://doi.org/10.1016/j.celrep.2023.113486"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37995182"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37995182"}]}]}]}