Notch Signaling: The Core Pathway and Its Posttranslational Regulation

Notch signaling controls numerous cell-fate specification events in multicellular organisms, and dysregulated Notch signaling causes several diseases with underlying developmental defects. A key step in Notch receptor activation is its intramembrane proteolysis, which releases an intracellular fragment that participates directly in transcriptional regulation of nuclear target genes. Despite the apparent simplicity of this mechanism, a host of posttranslational processes regulate Notch activity during its synthesis and secretion, ligand-dependent activation at the surface, endocytic trafficking, and degradation. This review describes the core developmental logic of Notch signaling and how regulatory mechanisms tailor Notch pathway outputs to specific developmental scenarios.