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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Journal ArticleDOI
Inhibition of hedgehog signalling prevents experimental fibrosis and induces regression of established fibrosis
Angelika Horn,Trayana Kireva,Katrin Palumbo-Zerr,Clara Dees,Michal Tomcik,Cinzia Cordazzo,Pawel Zerr,Alfiya Akhmetshina,Martial Ruat,Oliver Distler,Christian Beyer,Georg Schett,Jörg H W Distler +12 more
TL;DR: In this paper, the authors investigated inhibition of hedgehog signalling by targeting Smoothened (Smo) as a novel antifibrotic approach and found that hedgehog signaling is activated in SSc and in murine models of SSc.
Journal ArticleDOI
A phospho-dependent mechanism involving NCoR and KMT2D controls a permissive chromatin state at Notch target genes
Franz Oswald,Patrick Rodriguez,Benedetto Daniele Giaimo,Benedetto Daniele Giaimo,Zeus A. Antonello,Laura Mira,Gerhard Mittler,Verena N. Thiel,Kelly J. Collins,Nassif Tabaja,Wiebke Cizelsky,Melanie Rothe,Susanne J. Kühl,Michael Kühl,Francesca Ferrante,Kerstin Hein,Rhett A. Kovall,Maria Dominguez,Tilman Borggrefe +18 more
TL;DR: It is shown that the RBP-J interacting factor SHARP is not only able to interact with the NCoR corepressor complex, but also with the H3K4 methyltransferase KMT2D coactivator complex, revealing how signaling can fine-tune a committed chromatin state by phosphorylation of a pivotal chromatin-modifier.
Book ChapterDOI
Biodiversity and noncanonical Notch signaling.
TL;DR: Noncanonical Notch activities are focused on and correspond to the following: DSL-independent activations, interactions with non-DSL ligands, CSL-independent signaling, signal transduction without cleavage, differential posttranslational modifications, competition/protection for a cofactor, and cross talk with other signaling pathways.
Journal ArticleDOI
Transcriptional Maintenance of Pancreatic Acinar Identity, Differentiation and Homeostasis by PTF1A
Chinh Q. Hoang,Michael A. Hale,Ana C. Azevedo-Pouly,Hans Peter Elsässer,Tye G. Deering,Spencer G. Willet,Fong Cheng Pan,Mark A. Magnuson,Christopher V.E. Wright,Galvin H. Swift,Raymond J. MacDonald +10 more
TL;DR: Results showed that PTF1A maintains the expression of genes for all cellular processes dedicated to the production of the secretory digestive enzymes, a highly attuned surveillance of unfolded proteins, and a heightened unfolded protein response (UPR).
Journal ArticleDOI
Site-specific O-Glucosylation of the Epidermal Growth Factor-like (EGF) Repeats of Notch: EFFICIENCY OF GLYCOSYLATION IS AFFECTED BY PROPER FOLDING AND AMINO ACID SEQUENCE OF INDIVIDUAL EGF REPEATS*
TL;DR: It is demonstrated that proper folding of EGF repeats is essential for glycosylation by Poglut/Rumi, that alanine can substitute for proline in the context of coagulation factor 9 EGF repeat for O-glucose transfer, confirming the new consensus sequence, and that positively charged residues within the O- glucose consensus sequence reduce efficiency of glycosYLation byPoglut /Rumi.
References
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Journal ArticleDOI
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.
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
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.
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.
Journal ArticleDOI
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