Proteolytic Cleavage of Notch: “HIT and RUN”

Author(s): G. van Tetering, M. Vooijs

Journal Name: Current Molecular Medicine

Volume 11 , Issue 4 , 2011

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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.

Keywords: Notch cleavage, γ-secretase, ADAM metalloprotease, furin, presenilin, cancer, GSI (γ-secretase inhibitor), notch pathway, morphogenesis, homeostasis, neoplastic transformation, transcription factor, juxtamembrane, heterodimerization, mutations

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Article Details

Year: 2011
Published on: 01 March, 2012
Page: [255 - 269]
Pages: 15
DOI: 10.2174/156652411795677972
Price: $65

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