The Notch receptor signaling pathway is activated by the binding of the transmembrane receptor Notch (N) to transmembrane ligands, Dl or Ser, presented on adjacent cells. This results in the proteolytic cleavage of N, releasing the intracellular domain (NICD). NICD translocates into the nucleus, interacting with Su(H) and mam to form a transcription complex, which up-regulates transcription of Notch-responsive genes. Positive regulators of the pathway enhance the signal from the sending cell or the response in the receiving cell. (Adapted from FBrf0225731 and FBrf0192604).