fig1

Figure 1. Activation of the canonical Notch signaling pathway. Notch mediates the transmission of near- range signals by physical contact between adjacent cells. The sending signal cell expresses Notch ligands that bind to Notch receptors in the receiving signal cell. Upon binding, the intracellular portion of the Notch receptor undergoes sequential proteolytic cleavage by Adam enzymes and the γ-secretase complex. The cleavage by the γ-secretase complex frees the Notch intracellular domain (NICD) from the transmembrane Notch domain and it translocates to the nucleus. In the nucleus, NICD promotes a transcriptional switch by binding to RbpjK and displacing of co-repressors and promoting the recruitment of MAML proteins and other transcriptional activators, activating the gene transcription of Notch target genes of the Hes and Hey families.