fig2

Figure 2. The canonical Notch signaling pathway. In the signal-receiving cell, the Notch receptor precursor is cleaved (S1) by Furin-like convertase in the Golgi compartment, thereby producing Notch extracellular domain (NECD) and Notch transmembrane region (NTM). Upon ligand binding (DLL/JAGGED) expressed on signal-sending cell, NTM is cleaved (S2) by ADAM, resulting in Notch extracellular truncated intermediate (NEXT) exposition to γ-secretase complex cleavage (S3). S3 cleavage allows the release of Notch intracellular domain (NICD), which translocates to the nucleus and interacts with transcriptional regulators (MAML and CSL) to activate the Notch target genes (ON).