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. 2023 May 3;6(5):651–670. doi: 10.1021/acsptsci.2c00239

Figure 2.

Figure 2

Schematic of the Notch signaling pathway. (1) The Notch receptor processing takes place in the ER, by the enzyme O-fut (O-fucosyltransferase) that adds fucose to the Notch precursor. (2) In the trans-Golgi network, furin-like convertase cleaves full-length Notch (S1 cleavage) generating a heterodimer molecule, which is then glycosylated by Fringe proteins (3). (4) The heterodimer Notch receptors are then trafficked to the cell membrane. (5) Activation of Notch receptor takes place when a Delta/Serrate family of ligands binds to the extracellular receptor of Notch. (6) Upon ligand binding, S2 cleavage occurs by the ADAM protease (also known as TACE). (7) The ligand bound to the Notch extracellular domain (NECD) gets internalized by the signal sending cell and (8) gets degraded inside the lysosomes. (9) S3 cleavage occurs by the γ-secretase enzyme, which results in the release of the Notch intracellular domain (NICD) that gets internalized into the nucleus (10) and (11) binds to the DNA binding domain, CSL, thereby replacing the corepressors with the coactivators and facilitating the transcription of Notch targeted genes. (12) In the absence of NICD, the DNA binding domain, CSL, is bound to the corepressor complex, which inhibits the transcription of Notch targeted genes.