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
FOXP1 Promotes Embryonic Neural Stem Cell Differentiation by Repressing Jagged1 Expression
Luca Braccioli,Stephin J. Vervoort,Youri Adolfs,Cobi J. Heijnen,Onur Basak,R. Jeroen Pasterkamp,Cora H. Nijboer,Paul J. Coffer +7 more
TL;DR: A role for FOXP1 is supported in regulating embryonic NSC differentiation by modulating Notch signaling by repressing the expression of Notch pathway genes including the Notch-ligand Jagged1, resulting in inhibition of NotCh signaling.
Patent
Binding-triggered transcriptional switches and methods of use thereof
TL;DR: The present disclosure as mentioned in this paper provides binding-triggered transcriptional switch polypeptides, nucleic acids comprising nucleotide sequences encoding the binding triggered transcriptional switches, and host cells genetically modified with the nucleic acid.
Journal ArticleDOI
Antagonistic regulation of p57kip2 by Hes/Hey downstream of Notch signaling and muscle regulatory factors regulates skeletal muscle growth arrest
Antoine Zalc,Shinichiro Hayashi,Frédéric Auradé,Dominique Bröhl,Ted Hung-Tse Chang,Despoina Mademtzoglou,Philippos Mourikis,Zizhen Yao,Yi Cao,Carmen Birchmeier,Frédéric Relaix +10 more
TL;DR: A molecular mechanism whereby information provided by Hes/Hey downstream of Notch as well as MRF activities are integrated at the level of the p57kip2 enhancer to regulate the decision between progenitor cell maintenance and muscle differentiation is proposed.
Journal ArticleDOI
Histone lysine demethylases in breast cancer
TL;DR: It is determined that the expression of KDMs correlates with BC prognosis, and altering the interactions between KDMs and Polycomb Group genes (PcG) may provide novel avenues for therapy that specifically targets these genes in BC.
Journal ArticleDOI
A phase 1 dose escalation and expansion study of Tarextumab (OMP-59R5) in patients with solid tumors
David Smith,Rashmi Chugh,Amita Patnaik,Kyriakos P. Papadopoulos,Min Wang,Ann M. Kapoun,Lu Xu,Jakob Dupont,Robert Joseph Stagg,Anthony W. Tolcher +9 more
TL;DR: Tarextumab was generally well-tolerated at doses <2.5 mg weekly and 7.5-mg/kg on the every other and every three week schedules, and inhibition of Notch pathway signaling was demonstrated at these doses.
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.
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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