title: The molecular logic of Notch signaling--a structural and biochemical perspective.
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.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Wendy R
authors.initials: WR
authors.lastname: Gordon
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Arnett
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Blacklow
mesh_terms: 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
chemical_list: D008024:Ligands; D051880:Receptors, Notch
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