Figure 1.

Overview of Notch signalling. Mammalian Notch receptors expressed by mature T cells receive juxtacrine signals from four activating ligands (Jagged 1/2 or Delta-like 1/4) expressed on adjacent cells (either stromal cells in secondary lymphoid organs or professional antigen-presenting cells). Ligand/receptor binding triggers sequential proteolytic cleavage of the Notch receptor, first by the ADAM10 metalloprotease and then by the γ-secretase complex. These cleavages release intracellular Notch (ICN) into the cytoplasm where it enters the nucleus to form a transcriptional activation complex with the DNA-binding transcription factor RBP-Jκ and a member of the Mastermind-like (MAML) family, which in turn recruit additional transcriptional coactivators (CoA). The Notch transcriptional complex modifies chromatin structure to form clusters of enhancers and promoters and affect transcription. In some instances, ICN was reported to signal through non-canonical RBP-Jκ/MAML-independent pathways.