Journal ArticleDOI
Notch Signaling: Cell Fate Control and Signal Integration in Development
TLDR
Notch signaling defines an evolutionarily ancient cell interaction mechanism, which plays a fundamental role in metazoan development, providing a general developmental tool to influence organ formation and morphogenesis.Abstract:
Notch signaling defines an evolutionarily ancient cell interaction mechanism, which plays a fundamental role in metazoan development. Signals exchanged between neighboring cells through the Notch receptor can amplify and consolidate molecular differences, which eventually dictate cell fates. Thus, Notch signals control how cells respond to intrinsic or extrinsic developmental cues that are necessary to unfold specific developmental programs. Notch activity affects the implementation of differentiation, proliferation, and apoptotic programs, providing a general developmental tool to influence organ formation and morphogenesis.read more
Citations
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Journal ArticleDOI
Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexes
TL;DR: The crystal structure of a Notch transcriptional activation complex containing the ankyrin domain of human Notch1, the transcription factor CSL on cognate DNA, and a polypeptide from the coactivator Mastermind-like-1 is reported.
Journal ArticleDOI
Growth suppression of pre-T acute lymphoblastic leukemia cells by inhibition of notch signaling.
Andrew P. Weng,Yunsun Nam,Michael S. Wolfe,Warren S. Pear,James D. Griffin,James D. Griffin,Stephen C. Blacklow,Jon C. Aster +7 more
TL;DR: It is demonstrated here that the blockade of Notch signaling at two independent steps suppresses the growth and survival of NOTCH1-transformed T-ALL cells and identifies at least two steps in the NotCh signaling pathway as potential targets for chemotherapeutic intervention.
Journal ArticleDOI
Regulation of APP cleavage by α‐, β‐ and γ‐secretases
Janelle Nunan,David H. Small +1 more
TL;DR: The transmembrane aspartyl protease BACE has been identified as beta-secretase and several proteases (ADAM-10, TACE, PC7) may be alpha-secretases.
Journal ArticleDOI
Calcium depletion dissociates and activates heterodimeric notch receptors.
Matthew D. Rand,Lisa Grimm,Spyros Artavanis-Tsakonas,Vytas Patriub,Stephen C. Blacklow,Jeffrey Sklar,Jon C. Aster +6 more
TL;DR: Findings indicate that receptor activation can occur as a consequence of NEC dissociation, which relieves inhibition of the intrinsically active NTMsubunit.
Journal ArticleDOI
The Notch intracellular domain is ubiquitinated and negatively regulated by the mammalian Sel-10 homolog.
TL;DR: The data reveal the importance of ubiquitination and proteasome-mediated degradation for the activity and turnover of Notch ICs, and demonstrate that mSel-10 plays a key role in this process.
References
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Journal ArticleDOI
Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia
Anne Joutel,Christophe Corpechot,Anne Ducros,Katayoun Vahedi,Hugues Chabriat,Philippe Mouton,Sonia Alamowitch,Valérie Domenga,Michaelle Cécillion,Emmanuelle Maréchal,Jacqueline Maciazek,Céline Vayssière,Corinne Cruaud,E. A. Cabanis,Marie Madeleine Ruchoux,Jean Weissenbach,Jean Francois Bach,Marie-Germaine Bousser,Elisabeth Tournier-Lasserve +18 more
TL;DR: The characterization of the human Notch3 gene, which was previously mapped to the CADASIL critical region, is reported, indicating that Notch 3 could be the defective protein in CADASil patients.
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
Signalling downstream of activated mammalian Notch.
Sophie Jarriault,Christel Brou,Frédérique Logeat,Eric H. Schroeter,Raphael Kopan,Alain Israël +5 more
TL;DR: It is shown that activated forms of mNotch associate with the human analogue of Su(H), KBF2/RBP-JK and act as transcriptional activators through theKBF2-binding sites of the HES-1 promoter and block MyoD-induced myogenesis5-7.
Journal Article
Notch signaling : Signal transduction
TL;DR: The Notch/Lin-12/Glp-1 receptor family mediates the specification of numerous cell fates during development in Drosophila and Caenorhabditis elegans and putative components of the signaling cascade are identified, including a conserved family of extracellular ligands and two cellular factors that may associate with the Notch Intracellular domain.
Journal ArticleDOI
Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1
Linheng Li,Ian D. Krantz,Yu Deng,Yu Deng,Anna Genin,Amy B. Banta,Colin Collins,Ming Qi,Barbara J. Trask,Wen Lin Kuo,Joanne Cochran,Teresa Costa,Mary Ella M Pierpont,Elizabeth B. Rand,David A. Piccoli,Leroy Hood,Nancy B. Spinner +16 more
TL;DR: Four distinct coding mutations in JAG1 are demonstrated, providing evidence that it is the causal gene for Alagille syndrome, and supporting the hypothesis that haploinsufficiency for this gene is one of the mechanisms causing the Alagile syndrome phenotype.