Figure 1.

The Notch signalling pathway. (a) Schematic depiction of the major steps in the Notch processor maturation and routing in the cell. The Notch receptor is produced in the endoplasmic reticulum (ER) and the first proteolytic cleavage (S1) takes place in the Golgi compartment. After ligand interaction at the cell surface, S2 cleavage occurs. The Notch receptor subsequently undergoes S3 cleavage, at the cell surface or frequently in the endosome, and the resulting intracellular domain (ICD) is transported to the nucleus, where it becomes part of the ternary ICD/CSL/MAML transcriptional complex, which regulates downstream gene activation. (b) Schematic presentation of the proteolytic processing steps for the Notch receptor. The Notch receptor undergoes S1 cleavage in the heterodimerization domain (HD). S1 cleavage generates the extracellular domain (ECD) and the transmembrane/intracellular fragment (TMIC) moieties. The ECD is liberated into the extracellular space or taken up by the ligand-presenting cell, while the TMIC moiety is cleaved by S2 cleavage to form the Notch extracellular truncated (NEXT) domain. Finally, S3 cleavage in the membrane liberates the ICD (NICD), which is transported to the nucleus. PM, plasma membrane.