{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LARGE2 is a homolog of LARGE that functions as a bifunctional glycosyltransferase in the Golgi apparatus, where it catalyzes the sequential transfer of xylose and glucuronic acid moieties using UDP‐xylose and UDP‐glucuronic acid as donors. This enzymatic activity produces a repeating disaccharide polymer (“matriglycan”) that is essential for the functional glycosylation of α‐dystroglycan, conferring high‐affinity binding to extracellular matrix ligands such as laminin."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " LARGE2 supports the maturation of α‐dystroglycan more effectively than LARGE, and its overexpression enhances laminin receptor activity, whereas its downregulation leads to hypoglycosylation of α‐dystroglycan and consequent loss of extracellular matrix interactions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In addition, LARGE2 has been identified as a direct target of Wnt signaling in colonic epithelial and colorectal cancer cells, linking aberrant Wnt activity to enhanced LARGE2-dependent modification of α‐dystroglycan and increased cell–matrix adhesion that correlates with tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Studies in muscle and kidney further suggest that LARGE2 can compensate for defective LARGE function, highlighting its role in maintaining dystroglycan glycosylation across tissues and its potential as a therapeutic target in dystroglycanopathies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, recent evidence indicates that LARGE2 may extend its substrate repertoire beyond α‐dystroglycan to include proteoglycans, thereby broadening its impact on cell adhesion and extracellular matrix assembly."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Katsuya Fujimura, Hiromichi Sawaki, Tokiko Sakai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LARGE2 facilitates the maturation of alpha-dystroglycan more effectively than LARGE."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2005.02.082"}], "href": "https://doi.org/10.1016/j.bbrc.2005.02.082"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15752776"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15752776"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Angel Ashikov, Falk F R Buettner, Birgit Tiemann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LARGE2 generates the same xylose- and glucuronic acid-containing glycan structures as LARGE."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Glycobiology (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/glycob/cws153"}], "href": "https://doi.org/10.1093/glycob/cws153"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23135544"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23135544"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Alison K Esser, Michael R Miller, Qin Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of LARGE2 disrupts functional glycosylation of α-dystroglycan in prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.432807"}], "href": "https://doi.org/10.1074/jbc.M112.432807"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23223448"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23223448"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Qin Huang, Michael R Miller, James Schappet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The glycosyltransferase LARGE2 is repressed by Snail and ZEB1 in prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Biol Ther (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/15384047.2014.987078"}], "href": "https://doi.org/10.4161/15384047.2014.987078"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25455932"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25455932"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Vanessa Dietinger, Cira R García de Durango, Svenja Wiechmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Wnt-driven LARGE2 mediates laminin-adhesive O-glycosylation in human colonic epithelial cells and colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Commun Signal (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12964-020-00561-6"}], "href": "https://doi.org/10.1186/s12964-020-00561-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32586342"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32586342"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Kei-ichiro Inamori, Tobias Willer, Yuji Hara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endogenous glucuronyltransferase activity of LARGE or LARGE2 required for functional modification of α-dystroglycan in cells and tissues."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M114.597831"}], "href": "https://doi.org/10.1074/jbc.M114.597831"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25138275"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25138275"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Prabhjit K Grewal, Jennifer M McLaughlan, Christopher J Moore, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of the LARGE family of putative glycosyltransferases associated with dystroglycanopathies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Glycobiology (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/glycob/cwi094"}], "href": "https://doi.org/10.1093/glycob/cwi094"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15958417"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15958417"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Kei-Ichiro Inamori, Aaron M Beedle, Daniel Beltrán-Valero de Bernabé, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LARGE2-dependent glycosylation confers laminin-binding ability on proteoglycans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Glycobiology (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/glycob/cww075"}], "href": "https://doi.org/10.1093/glycob/cww075"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27496765"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27496765"}]}]}]}