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
Regulated Proteolysis of NOTCH2 and NOTCH3 Receptors by ADAM10 and Presenilins
Arjan J. Groot,Roger Habets,Sanaz Yahyanejad,Caroline M. Hodin,Karina Reiss,Paul Saftig,Jan Theys,Marc Vooijs +7 more
TL;DR: It is demonstrated that canonical ligand-induced proteolysis of the NOTCH1, -2, and -3 receptors strictly depends on consecutive cleavage of these receptors by ADAM10 and the presenilin-containing γ-secretase complex, leading to transcriptional activation.
Journal ArticleDOI
A dual role for NOTCH signaling in joint cartilage maintenance and osteoarthritis
Zhaoyang Liu,Zhaoyang Liu,Jianquan Chen,Anthony J. Mirando,Anthony J. Mirando,Cuicui Wang,Cuicui Wang,Michael J. Zuscik,Regis J. O'Keefe,Regis J. O'Keefe,Matthew J. Hilton,Matthew J. Hilton +11 more
TL;DR: A potential dual role for NOTCH in joint maintenance and osteoarthritis is investigated by generating two mouse models overexpressing the NOTCH1 intracellular domain (NICD) within postnatal joint cartilage and identifying downstream effectors of NOTCH signaling as potential targets for disease-modifying osteo arthritis drugs.
Journal ArticleDOI
PI3K/AKT Signaling Regulates H3K4 Methylation in Breast Cancer
Jennifer M. Spangle,Koen M.A. Dreijerink,Anna C. Groner,Hailing Cheng,Carolynn E. Ohlson,Jaime M. Reyes,Charles Y. Lin,James E. Bradner,Jean J. Zhao,Thomas M. Roberts,Myles Brown +10 more
TL;DR: The data identify a mechanism by which PI3K/AKT signaling modulates the cancer epigenome through controlling H3K4 methylation and suggest that KDM5A subcellular localization and genome occupancy may be pharmacodynamic markers of the activity of PI3k/AKt inhibitors currently in clinical development.
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Notch signaling in serous ovarian cancer.
TL;DR: Pre-clinical literature that links altered Notch signaling to ovarian cancer progression is focused on and several GSIs currently in phase I and II trials across many disease sites including ovary are reviewed.
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Lunatic Fringe-mediated Notch signaling is required for lung alveogenesis
Keli Xu,Erica Nieuwenhuis,Brenda L. Cohen,Wei Wang,Angelo J. Canty,Jayne S. Danska,Leigh Coultas,Janet Rossant,Megan Y.J. Wu,Tino D. Piscione,Andras Nagy,Andras Nagy,Achim Gossler,Geoff Hicks,Chi-chung Hui,R. Mark Henkelman,Lisa X. Yu,John G. Sled,Thomas Gridley,Sean E. Egan +19 more
TL;DR: It is demonstrated that Lfng functions to enhance Notch signaling in my ofibroblast precursor cells and thereby to coordinate differentiation and mobilization of myofibroblasts required for alveolar septation.
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.
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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.
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.
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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