Bare rudiments of notch signaling: how receptor levels are regulated

The Notch signaling pathway, a prototype for high-fidelity intercellular signaling mechanisms, regulates cell fate and other fundamental processes. Notch receptors are activated by transmembrane ligands present on neighboring cells through ligand-dependent proteolysis. This liberates the receptor intracellular domain, creating a transcriptional coactivator. Although tremendous progress towards elucidating the Notch activation mechanism and Notch-dependent processes has been reported, perhaps the most fundamental issue of Notch signaling is still poorly understood – how cell-type-specific Notch-receptor expression patterns are established and regulated. This is especially true for the four mammalian Notch receptors (Notch1–4), which exhibit unique and overlapping expression patterns. However, recent studies have demonstrated the transcriptional control of Notch receptor levels as an essential determinant of Notch signaling.