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J Cell Sci. 2008 Oct 1;121(Pt 19):3109-19. doi: 10.1242/jcs.035683.

The molecular logic of Notch signaling--a structural and biochemical perspective.

Author information

  • 1Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

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.

PMID:
18799787
[PubMed - indexed for MEDLINE]
PMCID:
PMC2696053
Free PMC Article

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