Notch Signal Transduction and Regulation

Notch is an evolutionarily conserved single-span transmembrane protein family that is used to regulate cell fate determinations during metazoan development. Notch signalling is mediated by a well-established mechanism that relies on a transmembrane ligand-induced release of the Notch intracellular domain (NICD) and the interaction of this fragment with the CSL (CBF1, Suppressor of Hairless, Lag-1) family of transcription factors within the nucleus. Level, duration and spatial distribution of Notch activity can be regulated through combination with intrinsic or extrinsic inducing factors at multiple levels including Notch-ligand interactions, trafficking and ubiquitination of Notch and ligands. The molecular components that participate in Notch signalling, central events of Notch signalling, multiple levels of Notch signal regulation and the relation with some human diseases are reviewed.