Figure 1.

A simplified view of canonical Notch signaling. Summary of the core signaling pathway created with BioRender.com. Canonical Notch ligands bind to the Notch receptors at epidermal growth factor (EGF) repeats 11–12 (dark green sections). Cleavage of the Notch receptor involves two proteolytic cleavage events, the first catalyzed by ADAM metalloproteases at the negative regulatory region (purple sections), the second by γ-secretase. This releases the Notch intracellular domain (NICD). In the nucleus, NICD interacts with DNA binding protein CBF1/Suppressor of Hairless/LAG1 (CSL; also known as RBPJ) and the coactivator Mastermind (MAM) to promote gene transcription.