Fig. 1. The Notch signaling pathway. The key players in this pathway are shown and consist of a Delta-type ligand, the receptor Notch and the CSL transcription factor. Delta and Notch are transmembrane proteins that contain extracellular arrays of EGF repeats (rectangles). The activation of Notch by its ligand triggers two proteolytic cleavages of Notch (S2 and S3). S3 cleavage releases the Notch intracellular domain (NICD, Notch^intra), which translocates to the nucleus and then activates CSL. The CSL co-repressor complex is displaced by a coactivator complex, containing NICD (Co-A, green), which mediates Notch target gene activation. In the absence of nuclear NICD, CSL associates with a co-repressor complex (Co-R, red), which actively represses the transcription of Notch target genes. Reproduced, with permission, from Lai (Lai, 2004).