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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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Differentiation of Effector CD4 T Cell Populations

TL;DR: This review summarizes the discovery, functions, and relationships among Th cells; the cytokine and signaling requirements for their development; the networks of transcription factors involved in their differentiation; the epigenetic regulation of their key cytokines and transcription factors; and human diseases involving defective CD4 T cell differentiation.
Journal ArticleDOI

Growth Factors, Matrices, and Forces Combine and Control Stem Cells

TL;DR: Multifaceted technologies are increasingly required to produce and interrogate cells ex vivo, to build predictive models, and, ultimately, to enhance stem cell integration in vivo for therapeutic benefit.
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MicroRNA control of signal transduction.

TL;DR: New evidence suggests that miRNAs affect the responsiveness of cells to signalling molecules such as transforming growth factor-β, WNT, Notch and epidermal growth factor, which serves as nodes of signalling networks that ensure homeostasis and regulate cancer, metastasis, fibrosis and stem cell biology.
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Balancing forces: architectural control of mechanotransduction

TL;DR: Sustained disruptions in tensional homeostasis can be caused by alterations in the extracellular matrix, allowing it to serve as a mechanically based memory-storage device that can perpetuate a disease or restore normal tissue behaviour.
References
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Journal ArticleDOI

SHARP is a novel component of the Notch/RBP‐Jκ signalling pathway

TL;DR: A model in which SHARP is a novel component of the HDAC corepressor complex, recruited by RBP‐Jκ to repress transcription of target genes in the absence of activated Notch is proposed.
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Notch activity acts as a sensor for extracellular calcium during vertebrate left–right determination

TL;DR: A mathematical model describing the dynamics of the Notch signalling pathway during chick embryo gastrulation is presented, which reveals a complex and highly robust genetic network that locally activates Notch on the left side of Hensen's node.
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Monoubiquitination and endocytosis direct γ-secretase cleavage of activated Notch receptor

TL;DR: It is demonstrated that a new modification, a monoubiquitination, as well as clathrin-dependent endocytosis, is required for γ-secretase processing of a constitutively active Notch derivative, ΔE, which mimics the TNFα-converting enzyme–processing product.
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The Notch ligand Delta1 is sequentially cleaved by an ADAM protease and γ-secretase

TL;DR: It is demonstrated here that the murine ligand Delta1 (Dll1) undergoes the same sequence of cleavages, in an apparently signal-independent manner, and that Dll1 is a substrate for regulated intramembrane proteolysis, and its intracellular region possibly fulfills a specific function in the nucleus.
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Instability of Hes7 protein is crucial for the somite segmentation clock.

TL;DR: In mice expressing mutant Hes7 with a longer half-life but normal repressor activity, somite segmentation and oscillatory expression became severely disorganized after a few normal cycles of segmentation; instability of Hes7 is essential for sustained oscillation and for its function as a segmentation clock.
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