Proteolytic Cleavage of Notch: "HIT and RUN"

G. van Tetering, M. Vooijs*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.
Original languageEnglish
Pages (from-to)255-269
JournalCurrent Molecular Medicine
Issue number4
Publication statusPublished - Jun 2011


  • Notch cleavage
  • gamma-secretase
  • ADAM metalloprotease
  • furin
  • presenilin
  • cancer
  • GSI (gamma-secretase inhibitor)


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