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The Notch pathway is an evolutionary conserved signaling system that regulates cell fate specification, tissue patterning and morphogenesis by modulating cell differentiation, proliferation, apoptosis and survival. In mammals, the core components of the pathway include five canonical DSL (Delta, Serrate, Lag2) ligands (called Dll1,3,4,andJagged1and2) and four single-pass transmembrane receptors (Notch1-4). Since the DSL ligands are membrane-bound, the Notch pathway relies on direct cell-cell interactions for signalgeneration. Ligand binding to the extracellular domain of Notch triggers the proteolytic activation of the
receptor. Juxtamembrane region cleavage of Notch by ADAM metalloproteinase is followed by ¦Ã-secretase complex-mediated cleavage and generation of the Notch intracellular domain (NICD). NICD then translocates to the nucleus, where it interacts with the
RBPJ/CSL transcription factor and induces the expression of Notch target genes such as the basic helixloop-helix proteins Hes and Hey.

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