Figure 2.

Notch signaling: an emerging therapeutic target for cancer treatment. Diagram—Notch receptor activation and therapeutic target in clinical development. Notch signaling is initiated by ligand binding to Notch receptor, which undergoes a two-step proteolytic cleavage by ADAM family proteases and γ-secretase, releasing the Notch intracellular domain (NICD). The NICD translocates to the nucleus where it binds to CSL and converts the complex from a repressor to an activator of Notch target genes. Notch signaling could be inhibited by two major classes of Notch inhibitors: γ-secretase inhibitors and monoclonal antibodies directing against Notch receptors or ligands. Fragment—NEXT, Notch extracellular truncated; CSL, C protein binding factor 1/Suppressor of Hairless/Lag-1; NEC, Notch extracellular subunit; NTM, Notch transmembrane.