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Notch signaling regulates many aspects of metazoan development and tissue renewal.
Accordingly, the misregulation or loss of Notch signaling underlies a wide range of
human disorders, from developmental syndromes to adult-onset diseases and cancer.
Notch signaling is remarkably robust in most tissues even though each Notch molecule
is irreversibly activated by proteolysis and signals only once without amplification
by secondary messenger cascades. In this Review, we highlight recent studies in Notch
signaling that reveal new molecular details about the regulation of ligand-mediated
receptor activation, receptor proteolysis, and target selection.