ArticleThe Journal of biological chemistry2010
Thermodynamic analysis of the CSL x Notch interaction: distribution of binding energy of the Notch RAM region to the CSL beta-trefoil domain and the mode of competition with the viral transactivator EBNA2.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- Bivalent interaction through an intrinsically disordered linker promotes transcription activation complex assembly in Notch signaling.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Signaling Mechanism of Budding, Proliferation, and Tissue Regeneration in Cnidaria.Current issues in molecular biology · 2025Review
- OptIC-Notch reveals mechanism that regulates receptor interactions with CSL.Development (Cambridge, England) · 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
- α-Phenylalanyl tRNA synthetase competes with Notch signaling through its N-terminal domain.PLoS genetics · 2022Article
- Review
- Information theoretic measures for quantifying sequence-ensemble relationships of intrinsically disordered proteins.Protein engineering, design & selection : PEDS · 2019Article
- Structurally conserved binding motifs of transcriptional regulators to notch nuclear effector CSL.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- The evolution of transcriptional repressors in the Notch signaling pathway: a computational analysis.Hereditas · 2019Article
- Epstein-Barr Virus Nuclear Antigen 3C Inhibits Expression ofJournal of virology · 2018Article
- OPTHiS Identifies the Molecular Basis of the Direct Interaction between CSL and SMRT Corepressor.Molecules and cells · 2018Article
- RBPJ/CBF1 interacts with L3MBTL3/MBT1 to promote repression of Notch signaling via histone demethylase KDM1A/LSD1.The EMBO journal · 2017Article
- Diffuse Staining for Activated NOTCH1 Correlates With NOTCH1 Mutation Status and Is Associated With Worse Outcome in Adenoid Cystic Carcinoma.The American journal of surgical pathology · 2017Article
- Control of transcriptional activity by design of charge patterning in the intrinsically disordered RAM region of the Notch receptor.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- KSHV and the Role of Notch Receptor Dysregulation in Disease Progression.Pathogens (Basel, Switzerland) · 2017Review
- Structure-function analysis of RBP-J-interacting and tubulin-associated (RITA) reveals regions critical for repression of Notch target genes.The Journal of biological chemistry · 2017Article
- Crystal structures of the ATP-binding and ADP-release dwells of the VNature communications · 2016Article
- RUNX super-enhancer control through the Notch pathway by Epstein-Barr virus transcription factors regulates B cell growth.Nucleic acids research · 2016Article
- Structure and function of the CSL-KyoT2 corepressor complex: a negative regulator of Notch signaling.Structure (London, England : 1993) · 2014Article
- Characterization of CSL (CBF-1, Su(H), Lag-1) mutants reveals differences in signaling mediated by Notch1 and Notch2.The Journal of biological chemistry · 2012Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The Notch signaling pathway is a cell-cell communication network giving rise to cell differentiation during metazoan development. Activation of the pathway releases the intracellular portion of the Notch receptor to translocate to the nucleus, where it is able to interact with the effector transcription factor CSL, converting CSL from a transcriptional repressor to an activator. This conversion is dependent upon the high affinity binding of the RAM region of the Notch receptor to the beta-trefoil domain (BTD) of CSL. Here we probe the energetics of binding to BTD of each conserved residue of RAM through the use of isothermal titration calorimetry and single residue substitution. We find that although the highly conserved PhiW PhiP motif is the largest determinant of binding, energetically significant interactions are contributed by N-terminal residues, including a conserved Arg/Lys-rich region. Additionally, we present a thermodynamic analysis of the interaction between the Epstein-Barr virus protein EBNA2 with BTD and explore the extent to which the EBNA2- and RAM-binding sites on BTD are nonoverlapping, as proposed by Fuchs et al. (Fuchs, K. P., Bommer, G., Dumont, E., Christoph, B., Vidal, M., Kremmer, E., and Kempkes, B. (2001) Eur. J. Biochem. 268, 4639-4646). Combining these results with displacement isothermal titration calorimetry, we propose a mechanism by which the PhiW PhiP motif of RAM and EBNA2 compete with one another for binding at the hydrophobic pocket of BTD using overlapping but specific interactions that are unique to each BTD ligand.
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Registered trials
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.