FIGURE 1.

Activation of Notch signalling. The Notch pathway can be activated in two ways, either by interacting with a ligand on an adjacent cell or following endocytosis driven by Deltex. S1 cleavage occurs in the Golgi and mediates the production of the mature Notch heterodimer which is presented on the surface of the cell. Ligand binding stimulates S2 cleavage, which causes the release of the Notch ectodomain and subsequent endocytosis by the ligand-presenting cell. S2 cleavage provides the substrate for γ-secretase, which carries out the final S3 cleavage and releases NICD into the cytoplasm where it can translocate into the nucleus to activate target gene transcription (Fortini, 2009; Aster et al., 2017). The endocytosis of the Notch protein to the multivesicular body driven by Deltex also provides a substrate for γ-secretase and thus target gene transcription (Steinbuck and Winandy, 2018).