FIGURE 1.

Notch signaling, structure, and activation: Mammal Notch system involved 4 receptors (Notch 1, Notch 2, Notch 3, and Notch 4) and 5 ligands of the Delta/Serrate/lag-2 (DSL) [Delta-like ligands (DLL-1, 3-4), Jagged1, and Jagged2]. Interaction between ligand and receptor expressed on adjacent cells induces two proteolytic events S2 and S3, catalyzed by ADAM-like metalloprotease and gamma-secretase complex, respectively. These two proteolytic events lead to the release of the intracellular active form of the receptor, i.e., NICD. NICD enters into the nucleus and forms a transactivation complex in association with partners, such as Master-mind like-1 (MALM1), Recombining binding protein suppressor of hairless/Core Binding Factor-1, Suppressor of Hairless, Lag-2 (RBP-jk/CSL). This transcription complex promotes the expression of genes of the helix basic family, including HES1, HEY1, and many other genes such as NF-κB, MYC and CCNDD.