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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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Structural and biochemical differences between the Notch and the amyloid precursor protein transmembrane domains.

TL;DR: In this paper, biochemical and structural data for the combined transmembrane and juxtamembrane Notch domains (Notch-TMD) that illuminate Notch signaling and that can be compared and contrasted with the corresponding traits of C99 are presented.
Journal ArticleDOI

Identification of novel targets of CSL-dependent Notch signaling in hematopoiesis.

TL;DR: Time course analysis of hematopoietic development revealed that cells with Notch 1 overexpression mimic miRNA expression of cells in a less mature stage, which is consistent with the previous biological characterization.
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mTORC1 is involved in hypoxia-induced pulmonary hypertension through the activation of Notch3

TL;DR: Pretreatment with the mTORC1 inhibitor rapamycin not only alleviated pulmonary arterial pressure and pulmonary arteriolar remodeling but also suppressed hypoxia‐induced m TORC1 and Notch3 activation, which indicates that both mTORc1 and notch3 signaling are involved in HPH and the downstream effects of mTOR C1 activation in HPh are partially dependent on the activation of Notch 3 signaling.
Journal ArticleDOI

Targeting the Notch signaling pathway in cancer therapeutics

TL;DR: There is a large body of evidence demonstrating that the Notch signaling pathway is critically involved in the pathobiology of a variety of malignancies, and an overview of emerging data is provided, which highlights the mechanism of the NotCh signaling pathway in the development of a wide range of cancers.
Journal ArticleDOI

Bioartificial Lung Engineering

TL;DR: A multidisciplinary collaborative effort will not only bring us closer to the ultimate goal of engineering patient‐derived lung grafts, but also generate a series of clinically valuable translational milestones such as airway grafts and disease models.
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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