Fig. 3

Schematic overview of the Notch signaling pathway. Ligands of the Jagged and Delta-like families interrelate with Notch family receptors on an adjacent cell. The Notch receptor exists at the cell surface as a proteolytically cleaved heterodimer containing of a large ectodomain and a membrane-tethered intracellular domain. The receptor-ligand interaction makes two additional proteolytic cleavages that free the Notch intracellular domain (NICD) from the cell membrane. The NICD moves to the nucleus, where it procedures a complex with the RBPJ protein, dislocating a histone deacetylase (HDAc)-co-repressor (CoR) complex from the RBPJ protein. Components of an activation complex, such as MAML1 and histone acetyltransferases (HAc), are engaged to the NICD-RBPJ complex, leading to the transcriptional activation of Notch target genes