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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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Early signaling events that underlie fate decisions of naive CD4 + T cells toward distinct T-helper cell subsets

TL;DR: How TCR‐mediated signals in collaboration with the cytokine environment influence the fate decisions of naive CD4+ T cells toward distinct Th subsets at the early stages of activation is reviewed.
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Inhibition of Notch Signaling in Glioblastoma Targets Cancer Stem Cells via an Endothelial Cell Intermediate

TL;DR: A novel three‐dimensional organotypic “explant” system of surgical GBM specimens that preserves cytoarchitecture and tumor stroma along with tumor cells is used and suggests a critical role for tumor endothelial cells in GBM stem cell maintenance, mediated at least in part by Notch signaling.
Journal ArticleDOI

Notch as a tumour suppressor.

TL;DR: This Review focuses on the latest developments relating specifically to the tumour-suppressor activity of Notch signalling and discusses the potential mechanisms by which Notch can inhibit carcinogenesis in various tissues.
Journal Article

Involvement of RBP-J in biological functions of mouse Notch1 and its derivatives

TL;DR: In this paper, the authors have compared the activities of mouse RAMIC and its derivatives in transactivation and differentiation suppression of myogenic precursor cells, and they have shown that differentiation suppression by Notch signalling is due to transactivation of genes carrying RBP-J binding motifs.
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A Role for the Primary Cilium in Notch Signaling and Epidermal Differentiation during Skin Development

TL;DR: Interestingly and independent of proliferation, ciliary mutants displayed defects in Notch signaling and commitment of progenitors to differentiate, and Shh signaling defects occurred later, arresting hair follicle morphogenesis in the skin.
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.
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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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