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
Notch and the Skeleton
TL;DR: Dysregulation of Notch signaling is the underlying cause of diseases affecting the skeletal tissue, including Alagille syndrome, spondylocostal dysostosis, and possibly, osteosarcoma.
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A combined ex vivo and in vivo RNAi screen for notch regulators in Drosophila reveals an extensive notch interaction network.
Abil Saj,Zeynep Arziman,Denise Stempfle,Werner van Belle,Ursula Sauder,Thomas Horn,Markus Dürrenberger,Renato Paro,Renato Paro,Michael Boutros,Gunter Merdes +10 more
TL;DR: A hitherto unappreciated diversity of tissue-specific modulators impinging on Notch is revealed and opens new avenues for studying Notch regulation and function in development and disease.
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TNF-induced osteoclastogenesis and inflammatory bone resorption are inhibited by transcription factor RBP-J
Baohong Zhao,Shannon N. Grimes,Susan Li,Xiaoyu Hu,Xiaoyu Hu,Lionel B. Ivashkiv,Lionel B. Ivashkiv +6 more
TL;DR: The Notch-driven transcription factor RBP-J inhibits osteoclast formation in response to TNF, and this inhibition is associated with down-regulation of TNF-related cell death in mice.
ComponentDOI
Recognition of the amyloid precursor protein by human gamma-secretase.
TL;DR: An atomic structure of human γ-secretase in complex with a transmembrane APP fragment at 2.6-angstrom resolution is reported, revealing contrasting features of substrate binding, which may be applied toward the design of substrate-specific inhibitors.
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Genome-wide analysis of N1ICD/RBPJ targets in vivo reveals direct transcriptional regulation of Wnt, SHH, and Hippo pathway effectors by Notch1
TL;DR: A transgenic mouse in which the activation of the Notch pathway massively expands the neural stem cell (NSC) pool in a cell context‐dependent manner is reported and direct interaction between Notch and Hippo‐Yap pathways in NSCs is shown.
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