Figure 2.

Schematic representation of the Notch signaling in mammals. Notch signaling is triggered upon ligand-receptor interaction which induces two sequential proteolytic cleavages, the first in the extracellular domain mediated by metalloproteases of the ADAM family, and the second within the transmembrane domain mediated by a γ-secretase activity of presenilins (PS). This second cleavage allows the release of the NICD, which translocates to the nucleus and associates with the CSL family transcription factor complex, resulting in subsequent activation of the notch target genes Hey and Hes family members.