Schematic representation of the NOTCH1 receptor. NOTCH1 is a class I transmembrane protein with a modular structure. The N-terminal EGF repeats are involved in interaction with Jagged and Δ-like ligands. The NRR holds the receptor inactive in the absence of ligand by limiting the access of the ADAM10 protease. Intracellular domains include the RAM (RBP-Jκ–associated module) and ANK (ankyrin repeat) domains involved in the interaction with the RBPJ DNA binding protein and the recruitment of transcriptional coactivators and the C-terminal PEST domain responsible for termination of NOTCH1 signaling by FBXW7-mediated proteasomal degradation.