ArticleMolecular biology of the cell2011
Structural and functional analysis of the repressor complex in the Notch signaling pathway of Drosophila melanogaster.
Article in Molecular biology of the cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
30 citing papers in PubMed, 55 citations in OpenAlex.
- Article
- Novel Genome-EngineeredGenes · 2024Article
- OptIC-Notch reveals mechanism that regulates receptor interactions with CSL.Development (Cambridge, England) · 2023Article
- Genetic and Molecular Interactions betweenGenes · 2023Article
- The Binding of CSL Proteins to Either Co-Activators or Co-Repressors Protects from Proteasomal Degradation Induced by MAPK-Dependent Phosphorylation.International journal of molecular sciences · 2022Article
- A Drosophila Su(H) model of Adams-Oliver Syndrome reveals cofactor titration as a mechanism underlying developmental defects.PLoS genetics · 2022Article
- Enhancers with cooperative Notch binding sites are more resistant to regulation by the Hairless co-repressor.PLoS genetics · 2021Article
- Biophysics of Notch Signaling.Annual review of biophysics · 2021Review
- Nucleo-cytoplasmic shuttling of murine RBPJ by Hairless protein matches that of Su(H) protein in the model system Drosophila melanogaster.Hereditas · 2021Article
- Phospho-Site Mutations in Transcription Factor Suppressor of Hairless Impact Notch Signaling Activity During Hematopoiesis inFrontiers in cell and developmental biology · 2021Article
- Article
- Limited Availability of General Co-Repressors Uncovered in an Overexpression Context during Wing Venation inGenes · 2020Article
- Structurally conserved binding motifs of transcriptional regulators to notch nuclear effector CSL.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- An RBPJ-Cells · 2019Article
- The evolution of transcriptional repressors in the Notch signaling pathway: a computational analysis.Hereditas · 2019Article
- Complex genetic interactions of novel Suppressor of Hairless alleles deficient in co-repressor binding.PloS one · 2018Article
- Phosphorylation of Suppressor of Hairless impedes its DNA-binding activity.Scientific reports · 2017Article
- Conservation of the Notch antagonist Hairless in arthropods: functional analysis of the crustacean Daphnia pulex Hairless gene.Development genes and evolution · 2017Article
- The Canonical Notch Signaling Pathway: Structural and Biochemical Insights into Shape, Sugar, and Force.Developmental cell · 2017Review
- Hairless-binding deficient Suppressor of Hairless alleles reveal Su(H) protein levels are dependent on complex formation with Hairless.PLoS genetics · 2017Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
In metazoans, the highly conserved Notch pathway drives cellular specification. On receptor activation, the intracellular domain of Notch assembles a transcriptional activator complex that includes the DNA-binding protein CSL, a composite of human C-promoter binding factor 1, Suppressor of Hairless of Drosophila melanogaster [Su(H)], and lin-12 and Glp-1 phenotype of Caenorhabditis elegans. In the absence of ligand, CSL represses Notch target genes. However, despite the structural similarity of CSL orthologues, repression appears largely diverse between organisms. Here we analyze the Notch repressor complex in Drosophila, consisting of the fly CSL protein, Su(H), and the corepressor Hairless, which recruits general repressor proteins. We show that the C-terminal domain of Su(H) is necessary and sufficient for forming a high-affinity complex with Hairless. Mutations in Su(H) that affect interactions with Notch and Mastermind have no effect on Hairless binding. Nonetheless, we demonstrate that Notch and Hairless compete for CSL in vitro and in cell culture. In addition, we identify a site in Hairless that is crucial for binding Su(H) and subsequently show that this Hairless mutant is strongly impaired, failing to properly assemble the repressor complex in vivo. Finally, we demonstrate Hairless-mediated inhibition of Notch signaling in a cell culture assay, which hints at a potentially similar repression mechanism in mammals that might be exploited for therapeutic purposes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.