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Fig. 1. Basic operation of the Notch pathway. The key players are a Delta-type ligand, the receptor Notch and the CSL transcription factor (see Table 1). Delta and Notch are transmembrane proteins containing extracellular arrays of EGF repeats (depicted by rectangles). Activation of Notch by its ligand triggers two proteolytic cleavages of Notch (S2 and S3, see also Box 2). S3 cleavage releases the Notch intracellular domain (Notch^intra), which translocates to the nucleus. Notch^intra activates CSL. The CSL co-repressor complex is displaced by a co-activator complex containing Notch^intra (Co-A, green icons), which mediates Notch target gene activation. In the absence of nuclear Notch^intra, CSL associates with a co-repressor complex (Co-R, red icons), which actively represses the transcription of Notch target genes.

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