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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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Journal ArticleDOI

Dissecting the mechanisms of Notch induced hyperplasia.

TL;DR: It is proposed that both the characteristics of the direct Notch targets and their cross‐regulatory relationships are important in coordinating the pattern of hyperplasia.
Journal ArticleDOI

Alteration of Notch signaling in skeletal development and disease.

TL;DR: These studies raise the question of how Notch may interact with other signaling pathways, such as Wnt, and manipulation of Notch signaling for bone‐related diseases remains complex because of the temporal and context‐dependent nature of notch signaling during mesenchymal stem cell and osteoblast differentiation.

Notch Pathway Is Activated by MAPK Signaling and Influences Papillary Thyroid

TL;DR: It is revealed that RET/PTC and BRAF(T1799A) activate Notch signaling and promote tumor growth in thyroid follicular cell and may be explored as an adjuvant therapy for thyroid papillary cancer.
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The interplay of the Notch signaling in hepatic stellate cells and macrophages determines the fate of liver fibrogenesis.

TL;DR: In vivo, post-disease treatment with Avagacestat significantly attenuated fibrogenesis in CCl4-induced liver fibrosis mouse model and suggest that Notch signaling plays a crucial role in HSC activation and M1/M2 polarization of macrophages in Liver fibrosis.
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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