Schematic of Notch signaling. Notch signaling is initiated by binding of the Notch transmembrance receptors with their specific ligands between two neighboring cells. Upon activation, Notch is cleaved, releasing the Notch intracellular domain (NICD) through cleavage by γ-secretase complex. The NICD can subsequently translocate into the nucleus for transcriptional activation of Notch target genes. When NICD enters the nucleus, co-repressors associated with CSL (CBF1, Suppressor of Hairless, Lag-1) are displaced and a transcriptionally active complex consisting of CSL, NICD, Mastermind, and other co-activators is formed, which converts CSL from a transcriptional repressor into an activator, leading to activation of Notch target genes.