title: Proteolytic cleavage of Notch: "HIT and RUN".
abstract: The Notch pathway is a highly conserved signaling pathway in multicellular eukaryotes essential in controlling spatial patterning, morphogenesis and homeostasis in embryonic and adult tissues. Notch proteins coordinate cell-cell communication through receptor-ligand interactions between adjacent cells. Notch signaling is frequently deregulated by oncogenic mutation or overexpression in many cancer types. Notch activity is controlled by three sequential cleavage steps leading to ectodomain shedding and transcriptional activation. Here we review the key regulatory steps in the activation of Notch, from receptor maturation to receptor activation (HIT) via a rate-limiting proteolytic cascade (RUN) in the context of species-specific differences.
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: van Tetering
authors.forename: M
authors.initials: M
authors.lastname: Vooijs
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002450:Cell Communication; D047108:Embryonic Development; D056890:Eukaryota; D045683:Furin / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D009024:Morphogenesis; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D053763:Presenilins / Q000235:genetics / Q000378:metabolism*; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013045:Species Specificity
chemical_list: D009842:Oligopeptides; D053763:Presenilins; D051880:Receptors, Notch; C523462:benzyloxycarbonyl-leucyl-leucyl-norleucinal; D053829:Amyloid Precursor Protein Secretases; D045683:Furin; D051722:ADAM Proteins