The NOTCH1 signaling pathway. Interaction of the NOTCH1 receptor with Delta-like and Jagged ligands expressed on the surface of a neighbor cells triggers the proteolytic cleavage of the receptor, first by an ADAM metalloprotease (S2 cleavage) and subsequently by the γ-secretase complex (S3 cleavage), which releases the intracellular domains of NOTCH1 (ICN1) from the membrane. ICN1 translocates to the nucleus and interacts with DNA via the RBPJ/CSL DNA binding protein and recruits the MAML1 coactivator to activate the expression of NOTCH1 target genes.