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. Author manuscript; available in PMC: 2022 Apr 12.
Published in final edited form as: Cancer Lett. 2019 Jul 18;461:123–131. doi: 10.1016/j.canlet.2019.07.012

Figure 3: Schematic representation of Notch receptor activation.

Figure 3:

Notch receptors are activated upon binding to Serrate- and Delta-like ligands present on the cell membranes of adjacent cells. Following successful activation, Notch receptors undergo a series of proteolytic cleavages at site 2 (S2), mediated by metalloprotease 10 (ADAM10) and TACE (TNFα converting enzyme). Additional proteolytic cleavages at the transmembrane domain (NTD) are carried out by a multi-subunit complex, γ-secretase, at site 3 (S3). The Notch intracellular domains (NICDs) are then released into the cytoplasm. The NICDs further translocate into the nucleus, where they displace histone deacetylase and co-repressors in CSL repressor complexes and recruit MAML1 and histone acetyltransferase p300 to form active transcriptional complexes, which regulate the transcriptional activity of Notch target genes.