Abstract
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 language | English (US) |
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Pages (from-to) | 3109-3119 |
Number of pages | 11 |
Journal | Journal of cell science |
Volume | 121 |
Issue number | 19 |
DOIs | |
State | Published - Oct 1 2008 |
Externally published | Yes |
Keywords
- Biological signaling
- Protein biochemistry
- Receptor
- Regulated intramembrane proteolysis
- Transcription