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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Effects of notch signaling on regulation of myeloid cell differentiation in cancer.
Pingyan Cheng,Vinit Kumar,Hao Liu,Je In Youn,Mayer Fishman,Simon Sherman,Dmitry I. Gabrilovich,Dmitry I. Gabrilovich +7 more
TL;DR: It is demonstrated that inhibition of Notch signaling in hematopoietic progenitor cells, myeloid-derived suppressor cells, and dendritic cells is directly involved in abnormalMyeloid cell differentiation in cancer.
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O-glucose trisaccharide is present at high but variable stoichiometry at multiple sites on mouse Notch1.
Nadia A. Rana,Aleksandra Nita-Lazar,Hideyuki Takeuchi,Shinako Kakuda,Kelvin B. Luther,Robert S. Haltiwanger +5 more
TL;DR: It is shown through biochemical and mass spectral analyses that serine is the only hydroxyamino acid that is modified with O-glucose on EGF repeats, and it is proposed that alanine N-terminal to cysteine 2: C1XSX(A/P)C2.
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Discrete Notch signaling requirements in the specification of hematopoietic stem cells
Albert D. Kim,Chase H. Melick,Wilson K. Clements,Wilson K. Clements,David L. Stachura,Martin Distel,Daniela Panáková,Daniela Panáková,Daniela Panáková,Calum A. MacRae,Lindsey Mork,J. Gage Crump,David Traver +12 more
TL;DR: It is demonstrated for the first time that multiple Notch signaling inputs are required to specify HSCs and that Notch3 performs a novel role within the somite to regulate the neighboring precursors of hemogenic endothelium.
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In Vivo Mapping of Notch Pathway Activity in Normal and Stress Hematopoiesis
Philmo Oh,Camille Lobry,Jie Gao,Anastasia N. Tikhonova,Evangelia Loizou,Jan Manent,Ben Van Handel,Sherif Ibrahim,Jeffrey Greve,Hanna K. A. Mikkola,Spyros Artavanis-Tsakonas,Spyros Artavanis-Tsakonas,Iannis Aifantis +12 more
TL;DR: These models provide comprehensive genetic maps of lineage-specific Notch receptor expression and activation in hematopoietic stem and progenitor cells and establish a previously unknown role for Notch signaling in the commitment of blood progenitors toward the erythrocytic lineage.
Journal ArticleDOI
NOTCH pathway inactivation promotes bladder cancer progression
Antonio Maraver,Pablo J. Fernandez-Marcos,Timothy P. Cash,Marinela Méndez-Pertuz,Marta Dueñas,Paolo Maietta,Paola Martinelli,Maribel Muñoz-Martin,Mónica Martínez-Fernández,Marta Cañamero,Giovanna Roncador,Jorge L. Martínez-Torrecuadrada,Dimitrios Grivas,José Luis de la Pompa,Alfonso Valencia,Jesús M. Paramio,Francisco X. Real,Manuel Serrano +17 more
TL;DR: Using bladder cancer cells, it is determined that the NOTCH pathway stabilizes the epithelial phenotype through its effector HES1 and, consequently, loss of NOTCH activity favors the process of epithelial-mesenchymal transition.
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.
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