The Canonical Notch Signaling Pathway: Unfolding the Activation Mechanism
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.About:
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.read more
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.
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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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Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1
Nishant Agrawal,Mitchell J. Frederick,Curtis R. Pickering,Chetan Bettegowda,Kyle Chang,Ryan J. Li,Carole Fakhry,Tong Xin Xie,Jiexin Zhang,Jing Wang,Nianxiang Zhang,Adel K. El-Naggar,Samar A. Jasser,John N. Weinstein,Lisa R. Trevino,Jennifer Drummond,Donna M. Muzny,Yuanqing Wu,Laura D. Wood,Ralph H. Hruban,William H. Westra,Wayne M. Koch,Joseph A. Califano,Joseph A. Califano,Richard A. Gibbs,Richard A. Gibbs,David Sidransky,Bert Vogelstein,Victor E. Velculescu,Nickolas Papadopoulos,David A. Wheeler,Kenneth W. Kinzler,Jeffrey N. Myers +32 more
TL;DR: To explore the genetic origins of head and neck squamous cell carcinoma, whole-exome sequencing and gene copy number analyses were used to study 32 primary tumors and identified mutations in FBXW7 and NotCH1, suggesting that NOTCH1 may function as a tumor suppressor gene rather than an oncogene in this tumor type.
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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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Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma membrane
TL;DR: Evidence is presented demonstrating that the Notch receptor on the plasma membrane is cleaved and two fragments are tethered together on the Plasma membrane by a link that is sensitive to reducing conditions, forming a heterodimeric receptor.
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Glycosylation regulates Notch signalling
Nicola Haines,Kenneth D. Irvine +1 more
TL;DR: This work has shown that extracellular post-translational modifications, in the form of glycosylation, are essential for the Notch signalling pathway, and that differences in the extent of glyCosylation are a significant mechanism by which this pathway is regulated.
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Mastermind Recruits CycC:CDK8 to Phosphorylate the Notch ICD and Coordinate Activation with Turnover
TL;DR: A role for MAM and CycC:CDK8 in the turnover of the Notch enhancer complex at target genes is suggested as well as point mutations affecting conserved Ser residues within the ICD PEST motif prevent hyperphosphorylation by Cyc: CDK8 and stabilize the I CD in vivo.
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Ligand endocytosis drives receptor dissociation and activation in the Notch pathway.
TL;DR: It is suggested that endocytosis into delta-expressing cells of NotchECD bound to delta plays a critical role during activation of the Notch receptor and is required to achieve processing and dissociation of the notch protein.
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Signal transduction by activated mNotch: importance of proteolytic processing and its regulation by the extracellular domain
TL;DR: It is demonstrated that a mNotch1 mutant protein that lacks its extracellular domain but retains its membrane-spanning region becomes proteolytically processed on its intracellular surface and, as a result, the activated intrACEllular domain (mNotchIC) is released and can move to the nucleus.
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Activating Mutations of NOTCH1 in Human T Cell Acute Lymphoblastic Leukemia
Andrew P. Weng,Andrew P. Weng,Adolfo A. Ferrando,Adolfo A. Ferrando,Woojoong Lee,Woojoong Lee,John P. Morris,John P. Morris,Lewis B. Silverman,Lewis B. Silverman,Cheryll Sanchez-Irizarry,Cheryll Sanchez-Irizarry,Stephen C. Blacklow,Stephen C. Blacklow,A. Thomas Look,A. Thomas Look,Jon C. Aster,Jon C. Aster +17 more