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Real-Time Imaging of Notch Activation with a Luciferase Complementation-Based Reporter

Sci. Signal.  12 Jul 2011:
Vol. 4, Issue 181, pp. rs7
DOI: 10.1126/scisignal.2001656

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Seeing Notch in Action

The Notch signaling pathway, which is critical for development and tissue renewal in adults, is complex, involving multiple ligand-induced cleavage events, translocation of cleaved active Notch fragments to the nucleus, and interactions with various partners to regulate gene expression. Ilagan et al. describe a luciferase complementation imaging assay system that enables monitoring of pathway activity in real time in live cells with high temporal resolution. They demonstrate not only the usefulness of this system for basic research into regulation of the activity of this pathway, but also the application of the system for high-throughput screening assays for the development and characterization of drugs that alter the activity of components in the pathway. Because enzymes that activate Notch are also involved in the production of amyloid β, which is implicated in Alzheimer’s disease, the system may prove useful for screening drugs that inhibit production of this toxic protein.