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
More filters
Journal ArticleDOI
Combined deficiency of Notch1 and Notch3 causes pericyte dysfunction, models CADASIL, and results in arteriovenous malformations
TL;DR: Notch is defined as a key regulator of pericyte function during angiogenesis and loss of pericyclete function due to Notch deficiency exacerbates endothelial cell activation caused by Notch1 haploinsufficiency.
Journal ArticleDOI
Fine-tuning of the intracellular canonical Notch signaling pathway.
Tilman Borggrefe,Robert Liefke +1 more
TL;DR: This review summarizes recent studies on transcriptional and chromatin control mechanisms, which set the stage for specific expression of Notch target genes and how the canonical (RBP-J dependent) Notch pathway is fine-tuned by downstream effectors and feedback loops in mammals.
Journal ArticleDOI
The Role of Notch Receptors in Transcriptional Regulation
TL;DR: The recent findings pertaining to the complex interplay between the Notch transcriptional complex and interacting factors involved in transcriptional regulation, including co‐activators, cooperating transcription factors, and chromatin regulators, are summarized and emerging data regarding the role of Notch‐regulated noncoding RNAs in transcription is discussed.
Journal ArticleDOI
Notch signaling and new therapeutic options in liver disease
TL;DR: Novel findings suggest that interfering with the aberrant activation of the Notch pathway may have therapeutic relevance, and further studies are needed to clarify the mechanisms regulating physiologic and pathologic Notch activation in the adult liver.
Journal ArticleDOI
γ-Secretase modulator (GSM) photoaffinity probes reveal distinct allosteric binding sites on presenilin.
Nikolay Pozdnyakov,Heather E. Murrey,Christina J. Crump,Christina J. Crump,Martin Pettersson,T. Eric Ballard,Christopher W. am Ende,Kwangwook Ahn,Kwangwook Ahn,Yue-Ming Li,Yue-Ming Li,Kelly R. Bales,Douglas S. Johnson +12 more
TL;DR: The photoaffinity probe E2012-BPyne specifically labels the N-terminal fragment of presenilin-1 (PS1-NTF) in cell membranes as well as in live cells and primary neuronal cultures providing evidence for multiple binding sites within γ-secretase that confer specific modulatory effects.
References
More filters
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.
Journal ArticleDOI
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