title: Jagged1 (JAG1): Structure, expression, and disease associations.
abstract: Jagged1 (JAG1) is one of the 5 cell surface ligands that functions primarily in the highly conserved Notch signaling pathway. Notch signaling plays a critical role in cellular fate determination and is active throughout development and across many organ systems. The classic JAG1-NOTCH interaction leads to a cascade of proteolytic cleavages resulting in the NOTCH intracellular domain being transported into the nucleus where it functions to activate downstream transcription of target genes. JAG1 mutations have been associated with several disorders including the multi-system dominant disorder Alagille syndrome, and some cases of tetralogy of Fallot (although these may represent variable expressivity of Alagille syndrome). In addition, variations in JAG1 have been found to be associated with multiple types of cancer including breast cancer and adrenocortical carcinoma. Alagille syndrome, which primarily affects the liver, heart, skeleton, eye, face, kidney and vasculature is caused by loss of function mutations in JAG1, demonstrating that haploinsufficiency for JAG1 is disease causing, at least in these tissues. Expression and conditional gene knockout studies of JAG1 (Jag1) have correlated with tissue-specific disease phenotypes and have provided insight into both disease pathogenesis and human development.
authors.affiliation: Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Grochowski
authors.affiliation: Division of Pediatric Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Loomes
authors.affiliation: Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: spinner@mail.med.upenn.edu.
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Spinner
mesh_terms: D016738:Alagille Syndrome / Q000235:genetics*; D002135:Calcium-Binding Proteins / Q000235:genetics*; D055785:Gene Knockdown Techniques; D020022:Genetic Predisposition to Disease; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D011666:Pulmonary Valve Stenosis / Q000235:genetics*; D000072099:Serrate-Jagged Proteins; D013771:Tetralogy of Fallot / Q000235:genetics*
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D000072099:Serrate-Jagged Proteins
keywords: Alagille syndrome; Developmental disorder; Jagged1; Notch signaling; Tetralogy of Fallot