Canonical and non-canonical Notch ligands

摘要: Notch signaling induced by canonical ligands is critical for normal embryonic development and tissue homeostasis through the regulation of a variety cell fate decisions cellular processes. Activation normally tightly controlled direct interactions with ligand-expressing cells, dysregulated associated developmental abnormalities cancer. While are responsible majority signaling, diverse group structurally unrelated noncanonical has also been identified that activate likely contribute to pleiotropic effects signaling. Soluble forms both have isolated, some which block could serve as natural inhibitors this pathway. Ligand activity can be indirectly regulated other pathways at level ligand expression, serving spatiotemporally compartmentalize integrate into molecular network orchestrates events. Here, we review mechanisms underlying dual role activators Additionally, evidence function independent presented. We discuss how posttranslational modification, endocytosis, proteolysis, spatiotemporal expression regulate their activity.