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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MiR-34a targeting of Notch ligand delta-like 1 impairs CD15+/CD133+ tumor-propagating cells and supports neural differentiation in medulloblastoma.
Pasqualino De Antonellis,Chiara Medaglia,Emilio Cusanelli,Immacolata Andolfo,Lucia Liguori,Gennaro De Vita,Marianeve Carotenuto,Annamaria Bello,Fabio Formiggini,Aldo Galeone,Giuseppe De Rosa,Antonella Virgilio,Immacolata Scognamiglio,Manuela Sciro,Giuseppe Basso,Johannes H. Schulte,Giuseppe Cinalli,Achille Iolascon,Massimo Zollo +18 more
TL;DR: Investigation of medulloblastoma tumors, which arise from an early impairment of developmental processes in the cerebellum, shows that stable nucleic-acid-lipid particles carrying mature miR-34a can target Dll1 in vitro and show equal effects to those of adenovirus miR -34a cell infection, and this technology forms the basis for their therapeutic use for the delivery of miR,34a in brain-tumor treatment.
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Dynamic compaction of human mesenchymal stem/precursor cells into spheres self-activates caspase-dependent IL1 signaling to enhance secretion of modulators of inflammation and immunity (PGE2, TSG6, and STC1)
TL;DR: It is demonstrated that MSC spontaneously aggregated into sphere‐like structures after injection into a subcutaneous air pouch or the peritoneum of mice, indicating that assembly of MSC into spheres triggers caspase‐dependent IL1 signaling and the secretion of modulators of inflammation and immunity.
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Abnormal recruitment of extracellular matrix proteins by excess Notch3ECD: a new pathomechanism in CADASIL
Marie Monet-Leprêtre,Marie Monet-Leprêtre,Iman Haddad,Céline Baron-Menguy,Céline Baron-Menguy,Maï Fouillot-Panchal,Maï Fouillot-Panchal,Meriem Riani,Meriem Riani,Valérie Domenga-Denier,Valérie Domenga-Denier,Claire Dussaule,Claire Dussaule,Emmanuel Cognat,Emmanuel Cognat,Joëlle Vinh,Anne Joutel,Anne Joutel +17 more
TL;DR: A dysregulation of TIMP3 activity is suggested, which could contribute to mutant Notch3(ECD) toxicity by impairing extracellular matrix homeostasis in small vessels and promoting the abnormal recruitment of functionally important extrace cellular proteins that may ultimately cause multifactorial toxicity.
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Crosstalk of Notch with p53 and p63 in cancer growth control.
TL;DR: This Opinion article focuses on the multilevel crosstalk between the Notch pathway and the p53 and p63 pathways, which are at the interface of external damaging signals and control of stem cell potential and differentiation.
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Inhibition Of Notch Activity Promotes Nonmitotic Regeneration of Hair Cells in the Adult Mouse Utricles
Vincent Lin,Justin S. Golub,Tot Bui Nguyen,Clifford R. Hume,Elizabeth C. Oesterle,Jennifer S. Stone +5 more
TL;DR: This study shows that mature mammals have a natural capacity to initiate vestibular hair cell regeneration and suggests that regional notch activity is a significant inhibitor of direct transdifferentiation of supporting cells into hair cells following damage.
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