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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Hey1 and Hey2 control the spatial and temporal pattern of mammalian auditory hair cell differentiation downstream of Hedgehog signaling.
TL;DR: Evidence is provided that in the murine cochlea, Hey1 and Hey2 control the spatiotemporal pattern of HC differentiation downstream of Hedgehog signaling, and this study identifies hedgehog signaling as a novel upstream regulator of their prosensory function in the mammalian coChlea.
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HES1 Promotes Colorectal Cancer Cell Resistance To 5-Fu by Inducing Of EMT and ABC Transporter Proteins.
Lei Sun,Jia Ke,Zhen He,Zexian Chen,Qinghua Huang,Wenjia Ai,Guo-qiang Wang,Yi-sheng Wei,Xiang-cai Zou,Shi Zhang,Ping Lan,Chu-yuan Hong +11 more
TL;DR: HES1 promotes chemoresistance to 5-Fu by prompting EMT and inducing of several ABC transporter genes, which might be a novel therapeutic target in CRC treatment.
Journal ArticleDOI
Monogenic causes of stroke: now and the future
Rhea Y. Y. Tan,Hugh S. Markus +1 more
TL;DR: This review covers single-gene disorders which lead to stroke as a major phenotype, with a focus on those which cause cerebral small vessel disease (SVD), an area where there has been significant recent progress with findings that may inform us about the pathogenesis of SVD more broadly.
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Mapping sites of O-glycosylation and fringe elongation on Drosophila Notch
Beth M. Harvey,Nadia A. Rana,Hillary Moss,Jessica Leonardi,Hamed Jafar-Nejad,Robert S. Haltiwanger +5 more
TL;DR: Mass spectral analysis on endogenous Notch purified from Drosophila embryos found that the glycosylation states were similar to those found on Notch from S2 cells, providing foundational information for future studies investigating the mechanisms of how O-glycosylations regulates Notch activity.
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The mammary cellular hierarchy and breast cancer
Samantha R. Oakes,Samantha R. Oakes,David Gallego-Ortega,David Gallego-Ortega,Christopher J. Ormandy,Christopher J. Ormandy +5 more
TL;DR: The discovery, definition and regulation of the mammary cellular hierarchy are reviewed, and recent advances in in vivo lineage tracing are outlined that are challenging many of the assumptions regarding the behavior of mammary stem cells.
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.
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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.
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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