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.