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Open AccessJournal ArticleDOI

The Canonical Notch Signaling Pathway: Unfolding the Activation Mechanism

Raphael Kopan, +1 more
- 17 Apr 2009 - 
- Vol. 137, Iss: 2, pp 216-233
TLDR
This Review highlights recent studies in Notch signaling that reveal new molecular details about the regulation of ligand-mediated receptor activation, receptor proteolysis, and target selection.
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This article is published in Cell.The article was published on 2009-04-17 and is currently open access. It has received 3120 citations till now. The article focuses on the topics: Notch signaling pathway & Notch 1.

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Citations
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Neural stem cell quiescence and stemness are molecularly distinct outputs of the Notch3 signalling cascade in the vertebrate adult brain

TL;DR: It is demonstrated that quiescence and stemness are molecularly distinct outputs of Notch3 signalling, and Hey1 is identified as a major NotCh3 effector controlling NSC stemness in the vertebrate adult brain.
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Notch Signaling Promotes Growth and Invasion in Uveal Melanoma

TL;DR: It is suggested that Notch plays an important role in inducing proliferation and invasion in uveal melanoma and that inhibiting this pathway may be effective in preventing tumor growth and metastasis.
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Understanding the Principles of Pattern Formation Driven by Notch Signaling by Integrating Experiments and Theoretical Models.

TL;DR: Experimental and computational models that help understand the operating principles of cell patterning driven by Notch signaling are reviewed and some recent evidence of mechanosensitivity in the Notch pathway in driving collective epithelial cell migration and cardiovascular morphogenesis is discussed.
References
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Journal ArticleDOI

Notch signalling: a simple pathway becomes complex

TL;DR: Although the intracellular transduction of the Notch signal is remarkably simple, with no secondary messengers, this pathway functions in an enormous diversity of developmental processes and its dysfunction is implicated in many cancers.
Journal ArticleDOI

Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain.

TL;DR: It is shown that signalling by a constitutively active membrane-bound Notch-1 protein requires the proteolytic release of the Notch intracellular domain (NICD), which interacts preferentially with CSL.
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Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells.

TL;DR: This work shows a rapid, massive conversion of proliferative crypt cells into post-mitotic goblet cells after conditional removal of the common Notch pathway transcription factor CSL/RBP-J and indicates that γ-secretase inhibitors, developed for Alzheimer's disease, might be of therapeutic benefit in colorectal neoplastic disease.
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