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. 2021 Jun 7;11(6):849. doi: 10.3390/biom11060849

Figure 2.

Figure 2

Trans-interaction of receptor and ligand activation of Notch signaling results in the transcription of CBF1-bound Notch target genes. Interaction of DELTA-LIKE1 (DLL1) DSL domain with the 10th and 11th EGF-like domain activates endocytosis by the source cell. This exposes the S2 site for cleavage by ADAM10 or TACE. Prior to Notch activation, Notch target genes are silenced by the recruitment of corepressors to CBF1. S2 cleavage exposes key amino acids to S3 cleavage by γ-secretase, releasing NIC1 into the nucleus of the target cell. NIC1 binds to CBF1 and displaces corepressors to upregulate Notch target gene expression. ADAM10: A disintegrin and metalloprotease 10; CBF1: C-promoter binding factor 1 (also termed RBPjκ); EGF-like: Epidermal growth factor-like; NIC1: Intracellular domain of NOTCH1; TACE: ADAM17/Tumor necrosis factor-α converting enzyme.