Figure 4.

Notch signaling process. Following receptor–ligand binding, sequential S2- and S3-cleavage of the Notch intracellular domain (NICD, yellow) allows the cleaved protein to enter the nucleus, whereas the (red) ligand–Notch extracellular domain (NECD, blue) complex is transendocytosed into a ligand-presenting cell. Nuclear NICD is associated with the DNA-binding protein RBPjk, followed by detachment of the co-repressor and recruitment of the co-activator, resulting in target gene activation.