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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Notch in the kidney: development and disease
Yasemin Sirin,Katalin Susztak +1 more
TL;DR: Notch signalling is markedly reduced in the adult kidney; however, increased Notch signalling has been noted in both acute and chronic kidney injury, indicating that Notch is a key regulator of kidney development, repair, and injury.
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F-box and WD Repeat Domain-Containing 7 Regulates Intestinal Cell Lineage Commitment and Is a Haploinsufficient Tumor Suppressor
TL;DR: FbW7 regulates intestinal biology and tumorigenesis by controlling the abundance of different substrates in a dose-dependent fashion, providing a molecular explanation for the heterozygous mutations of fbw7 observed in human colorectal carcinoma.
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Inhibition of Notch signaling prevents experimental fibrosis and induces regression of established fibrosis
Clara Dees,Pawel Zerr,Michal Tomcik,Michal Tomcik,Christian Beyer,Angelika Horn,Alfiya Akhmetshina,Katrin Palumbo,Nicole Reich,Jochen Zwerina,Michael Sticherling,Mark P. Mattson,Oliver Distler,Georg Schett,Jörg H W Distler +14 more
TL;DR: It is demonstrated that pharmacologic as well as genetic inhibition of Notch signaling exerts potent antifibrotic effects in different murine models of SSc and might have direct translational implications because different inhibitors of the γ-secretase complex are available and have yielded promising results in cancer trials.
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Hypo- and hyperactivated Notch signaling induce a glycolytic switch through distinct mechanisms
Sebastian K.-J. Landor,Sebastian K.-J. Landor,Sebastian K.-J. Landor,Anders P. Mutvei,Veronika Mamaeva,Veronika Mamaeva,Shaobo Jin,Morten Busk,Ronald Borra,Tove J. Grönroos,Pauliina Kronqvist,Urban Lendahl,Cecilia Sahlgren,Cecilia Sahlgren +13 more
TL;DR: It is shown that Notch signaling is a key regulator of cellular metabolism and required for metabolic flexibility, and a role for Notch in cellular energy homeostasis is revealed.
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C8orf4 negatively regulates self-renewal of liver cancer stem cells via suppression of NOTCH2 signalling
TL;DR: C8orf4 negatively regulates the self-renewal of liver CSCs via suppression of NOTCH2 signalling and activation levels are consistent with clinical severity and prognosis of HCC patients.
References
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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
TL;DR: These findings greatly expand the role of activated NOTCH1 in the molecular pathogenesis of human T-ALL and provide a strong rationale for targeted therapies that interfere with NOTCH signaling.
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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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An Essential Role for Ectodomain Shedding in Mammalian Development
Jacques J. Peschon,Jennifer L. Slack,Pranitha Reddy,Kim L. Stocking,Susan W. Sunnarborg,David C. Lee,William E. Russell,Beverly J. Castner,Richard S. Johnson,Jeffrey N. Fitzner,Rogely W. Boyce,Nicole Nelson,Carl J. Kozlosky,Martin F. Wolfson,Charles Rauch,Douglas P. Cerretti,Raymond J. Paxton,Carl J. March,Roy A. Black +18 more
TL;DR: The phenotype of mice lacking TACE suggests an essential role for soluble TGFalpha in normal development and emphasizes the importance of protein ectodomain shedding in vivo.
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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.
Johan H. van Es,Marielle E. van Gijn,Orbicia Riccio,Maaike van den Born,Marc Vooijs,Harry Begthel,Miranda Cozijnsen,Sylvie Robine,Doug J. Winton,Freddy Radtke,Hans Clevers +10 more
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.
Related Papers (5)
Notch Signaling: Cell Fate Control and Signal Integration in Development
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