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Trends Biochem Sci. 2007 Oct;32(10):477-85.

Bare rudiments of notch signaling: how receptor levels are regulated.

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  • 1University of Wisconsin School of Medicine, Department of Pharmacology, 385 Medical Sciences Center, Madison, WI 53706, USA.


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.

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