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Jagged-1 (JAG1)
- Target
- JAG1
- Molecular classification
- Ligand (Notch pathway), Receptor ligand, Membrane protein, Signaling molecule
01
Overview
Jagged-1 (JAG1) is a transmembrane ligand protein that binds and activates Notch receptors (NOTCH1-4) across various tissues in mammals. It consists of an extracellular domain (with a DSL domain, 16 EGF-like repeats, and a cysteine-rich region), a transmembrane segment, and a small intracellular domain. Through Notch interaction, Jagged-1 governs critical cell fate decisions during development, regulates transcription via the canonical Notch pathway, and is implicated in several diseases, including Alagille syndrome (from JAG1 mutation) and various cancers. Some evidence suggests Jagged-1 itself, beyond acting as a Notch ligand, can undergo proteolytic cleavage and form an intracellular domain with distinct transcriptional activities in cancer.
- Other names
- JAG1CD339Jagged1
02
Mechanism of action
Inhibition of Notch pathway activation (by blocking Jagged-1/Notch1 interaction or downstream cleavage via γ-secretase inhibition); Antagonism of ligand-receptor binding
03
Biological functions
Signal transduction (via Notch pathway)Cell fate determinationCell proliferationApoptosisEmbryonic developmentCell differentiationTranscriptional regulation (via intracellular domain activity)
04
Disease associations
Cancer (multiple types; correlates with progression, invasion, and metastasis)Developmental disorder (Alagille syndrome, congenital heart defects including Tetralogy of Fallot)Cardiovascular diseaseLiver disease
05
Safety considerations
Notch pathway inhibition: broad tissue effects, developmental and cancer risksOn-target toxicity (Notch signaling is essential in many tissues; inhibition can lead to unwanted effects in liver, heart, and gastrointestinal tract)Off-target toxicity (if drugs are non-specific)
06
Interacting drugs
Gamma-secretase inhibitors
1 more in the full profile.
07
Biomarkers
JAG1 expression (used as biomarker for some cancers, poor prognosis)JAG1 mutation (diagnostic for Alagille syndrome)
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