Protein Jagged-1 (JAG1) (JAG1)

Protein Jagged-1 (JAG1) is a single-pass type I transmembrane protein that serves as a primary ligand for Notch receptors, specifically Notch 1, 2, and 3 (UniProt P78504). It is a critical component of the Notch signaling pathway, which governs cell-fate determination, proliferation, and differentiation during both embryonic development and adult tissue homeostasis (PubMed: 30105235). Mutations in the JAG1 gene are the primary cause of Alagille syndrome, a multisystem disorder characterized by liver bile duct paucity, heart defects, and skeletal abnormalities (NIH MedlinePlus). In oncology, JAG1 is frequently overexpressed in various solid tumors, including breast, colorectal, and hepatocellular carcinoma, where it promotes epithelial-mesenchymal transition (EMT), angiogenesis, and the maintenance of cancer stem cells (PubMed: 28655779). Therapeutic strategies targeting JAG1 include monoclonal antibodies like Demcizumab, which block ligand-receptor interaction, and experimental RNA-based therapies designed to silence JAG1 mRNA expression (PubMed: 25103560). However, the clinical development of JAG1 inhibitors has faced challenges due to on-target toxicities, particularly gastrointestinal issues like goblet cell metaplasia, resulting from systemic Notch pathway inhibition (PubMed: 23636131).

Other names

Jagged1JAGL1HJ1CD339AGSAHDAWSAlagille syndrome protein

Inhibition of Notch signaling by blocking the interaction between the Jagged-1 ligand and Notch receptors, or by reducing JAG1 expression via RNA interference (PubMed: 25103560).