Notch ligand, JAG1, is evolutionarily conserved target of canonical WNT signaling pathway in progenitor cells

摘要: WNT, Notch, FGF, and Hedgehog signaling pathways network together during embryogenesis, tissue regeneration, carcinogenesis. Association of Notch ligands with receptors on neighboring cells leads to cleavage by metalloprotease gamma-secretase induce nuclear translocation intracellular domain (NICD). Nuclear complex, consisting CSL (RBPSUH), NICD, Mastermind (MAML), p300 histone acetyltransferase (HAT), then induces transcriptional activation target genes, such as HES1, HES5, HES7, HEY1, HEY2 HEYL. Here, we searched for TCF/LEF-binding site within the promoter region ligand including DLL1, DLL3, DLL4, JAG1 JAG2. Because sites were identified human based bioinformatics intelligence, comparative genomics analyses orthologs further performed. Chimpanzee gene, 26 exons, was NW_120319.1 genome sequence. XM_525264.1 XM_514517.1 not correct coding sequences chimpanzee JAG1. gene found encode a 1218-amino-acid protein showing 99.5% 96.2% total-amino-acid identity mouse Jag1, respectively. Phylogenetic analysis revealed that more conserved than those other ligands. evolutionarily WNT/beta-catenin pathway conservation double 5'-promoter mammalian orthologs. Human mRNA expressed in embryonic stem (ES) cells, neural tissues, lung carcinoid, gastric cancer, pancreatic colon also squamous cell carcinoma (SCC) skin, oral cavity, esophagus, head neck. expression progenitor due canonical WNT self-renewal activation. JAG1, functioning WNT-dependent activator, is key molecule maintaining homeostasis cells.