The molecular logic of Notch signaling--a structural and biochemical perspective.
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.
Gordon
Wendy R
WR
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Arnett
Kelly L
KL
Blacklow
Stephen C
SC
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D008024:Ligands; D021381:Protein Transport; D051880:Receptors, Notch / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
D008024:Ligands; D051880:Receptors, Notch
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