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
Roles of Drosophila deltex in Notch receptor endocytic trafficking and activation.
Kenta Yamada,Takashi J. Fuwa,Tomonori Ayukawa,Tsubasa Tanaka,Akira Nakamura,Marian B. Wilkin,Martin Baron,Kenji Matsuno +7 more
TL;DR: Investigation of N endocytosis in a dx‐null Drosophila mutant found that endogenous Dx is required for at least two steps of N trafficking: the incorporation of N into endocytic vesicles from the plasma membrane and the transport of N from early endosomes to lysosomes.
Journal ArticleDOI
Structure and Function of the CSL-KyoT2 Corepressor Complex: A Negative Regulator of Notch Signaling.
TL;DR: The structure and function of CSL in complex with the corepressor KyoT2 is characterized using a combination of structural, biophysical, and cellular approaches to provide molecular insights into how K yoT2 binds CSL with high affinity and competes with coactivators, such as Notch, for binding CSL.
Journal ArticleDOI
Notch-Tnf signalling is required for development and homeostasis of arterial valves.
Yidong Wang,Bingruo Wu,Emily J. Farrar,Wendy Lui,Pengfei Lu,Donghong Zhang,Christina M. Alfieri,Kai Mao,Ming Chu,Di Yang,Di Xu,Michael Rauchman,Verdon Taylor,Simon J. Conway,Katherine E. Yutzey,Jonathan T. Butcher,Bin Zhou,Bin Zhou +17 more
TL;DR: It is shown that Notch-Tnf signalling balances proliferation and apoptosis for post-EMT development of arterial valves and suggested that mutations in its components may lead to congenital anomaly of aortic valves and valvar stenosis in humans.
Posted ContentDOI
Discovery and characterization of coding and non-coding driver mutations in more than 2,500 whole cancer genomes
Esther Rheinbay,Morten Muhlig Nielsen,Federico Abascal,Grace Tiao,Henrik Hornshøj,Julian M. Hess,Randi Istrup Istrup Pedersen,Lars Feuerbach,Radhakrishnan Sabarinathan,Henrik Tobias Madsen,Jaegil Kim,Loris Mularoni,Shimin Shuai,Andrés Arturo Lanzós Camaioni,Carl Herrmann,Yosef E. Maruvka,Ciyue Shen,Samir B. Amin,Johanna Bertl,Priyanka Dhingra,Klev Diamanti,Abel Gonzalez-Perez,Qianyun Guo,Nicholas J. Haradhvala,Keren Isaev,Malene Juul,Jan Komorowski,Sushant Kumar,Dong-Hoon Lee,Lucas Lochovsky,Eric Minwei Liu,Oriol Pich,David Tamborero,Husen M. Umer,Liis Uusküla-Reimand,Claes Wadelius,Lina Wadi,Jing Zhang,Keith A. Boroevich,Joana Carlevaro-Fita,Dimple Chakravarty,Calvin Wing Yiu Chan,Nuno A. Fonseca,Mark P. Hamilton,Chen Hong,André Kahles,Young-Wook Kim,Kjong-Van Lehmann,Todd A. Johnson,Abdullah Kahraman,Keunchil Park,Gordon Saksena,Lina Sieverling,Nicholas A Sinnott-Armstrong,Peter J. Campbell,Asger Hobolth,Manolis Kellis,Michael S. Lawrence,Ben Raphael,Mark A. Rubin,Chris Sander,Lincoln Stein,Josh Stuart,Tatsuhiko Tsunoda,David A. Wheeler,Rory Johnson,Jüri Reimand,Mark Gerstein,Ekta Khurana,Nuria Lopez-Bigas,Inigo Martincorena,Jakob Skou Pedersen,Gad Getz,Pcawg Drivers,Icgc +74 more
TL;DR: These analyses redefine the landscape of non-coding driver mutations in cancer genomes, confirming a few previously reported elements and raising doubts about others, while identifying novel candidate elements across 27 cancer types.
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Notch signaling as a therapeutic target for breast cancer treatment
TL;DR: There are many remaining uncertainties that must be addressed experimentally if there are to exploit inhibition of Notch signaling as a treatment approach in breast cancer, but Notch inhibition, in combination with other therapies, is a promising avenue for future management of breast cancer.
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.
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