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. 2019 Oct 16;10(10):815. doi: 10.3390/genes10100815

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© 2019 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Notch signaling pathway by ubiqutination upon binding of Jagged/Delta (JAG/DLL) ligands to the Notch receptor (N1); the endocytic system is activated in the ligand-bearing cell. This leads to two sequential proteolytic events. The first is metalloproteinase-dependent (ADAM10/17) and it releases the extracellular domain of the Notch receptor which is afterward engulfed via transendocytosis. The second proteolytic cleavage is membrane bound and dependent on γ-secretase activity. After this step, NICD (the Notch intracellular part) is released to the cytosol and transported to the nucleus where it interacts with the CSL/RBP-Jκ transcription factor and its co-factor Mastermind (MAML1). The complex is tethered to promoters of Notch target genes. For details see the text.