Notch Regulation of Hematopoiesis, Endothelial Precursor Cells, and Blood Vessel Formation: Orchestrating the Vasculature

Figure 1

Mammalian cells are equipped with 4 Notch receptors (Notch1-4) and five ligands (Jag1,2 and Dll1,3,4). Notch signaling is triggered upon receptor-ligand interaction, which induces two sequential proteolytic cleavages. The first cleavage, in the extracellular domain, is catalyzed by ADAM metalloproteinases, and the second, within the membrane domain, is facilitated by the γ-secretase complex. This second cleavage allows the release and translocation of the Notch intracellular domain (NICD) to the nucleus. Binding of NICD to cotranscription factor RBPjk leads to transcriptional activation of the Notch target genes HES and HERP/HEY by displacement of a corepressor (CoR) and recruitment of the coactivator, mastermind-like protein (MAML1).