The molecular logic of Notch signaling - A structural and biochemical perspective

Wendy R. Gordon, Kelly L. Arnett, Stephen C. Blacklow

Research output: Contribution to journalArticlepeer-review

205 Scopus citations


The Notch signaling pathway constitutes an ancient and conserved mechanism for cell-cell communication in metazoan organisms, and has a central role both in development and in adult tissue homeostasis. Here, we summarize structural and biochemical advances that contribute new insights into three central facets of canonical Notch signal transduction: (1) ligand recognition, (2) autoinhibition and the switch from protease resistance to protease sensitivity, and (3) the mechanism of nuclear-complex assembly and the induction of target-gene transcription. These advances set the stage for future mechanistic studies investigating ligand-dependent activation of Notch receptors, and serve as a foundation for the development of mechanism-based inhibitors of signaling in the treatment of cancer and other diseases.

Original languageEnglish (US)
Pages (from-to)3109-3119
Number of pages11
JournalJournal of cell science
Issue number19
StatePublished - Oct 1 2008
Externally publishedYes


  • Biological signaling
  • Protein biochemistry
  • Receptor
  • Regulated intramembrane proteolysis
  • Transcription


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