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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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Mechanisms of lung development: contribution to adult lung disease and relevance to chronic obstructive pulmonary disease.

TL;DR: The role of selected pathways, including Sonic hedgehog, Notch, retinoid, and Tgf beta in the developing lung and the potential association with COPD are discussed.
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Inhibitory effect of curcumin on oral carcinoma CAL‐27 cells via suppression of Notch‐1 and NF‐κB signaling pathways

TL;DR: It is concluded that the down‐regulation of Notch‐1 by curcumin could be an effective approach, which will cause down‐ regulation of NF‐κB, resulting in the inhibition of cell growth and invasion.
Journal ArticleDOI

Metabolic Regulation of Adipose Tissue Macrophage Function in Obesity and Diabetes.

TL;DR: This review focuses on the role of macrophages in AT inflammation and obesity, and the metabolic changes in macrophage function that occur with activation that underpin their role in the pathogenesis of IR and T2D.
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Jagged1 (JAG1): Structure, expression, and disease associations.

TL;DR: Alagille syndrome, which primarily affects the liver, heart, skeleton, eye, face, kidney and vasculature is caused by loss of function mutations in JAG1, demonstrating that haploinsufficiency for Jag1 is disease causing, at least in these tissues.
Journal ArticleDOI

Notch Signaling Activation as a Hallmark for Triple-Negative Breast Cancer Subtype.

TL;DR: The purpose of this up-to-date review is to provide a detailed overview of the specific role of all four Notch receptors in TNBCs, thus identifying the Notch signaling pathway deregulation/activation as a pathognomonic feature of this breast cancer subtype.
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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