ArticleThe Journal of biological chemistry2017
Structure-function analysis of RBP-J-interacting and tubulin-associated (RITA) reveals regions critical for repression of Notch target genes.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Deciphering and targeting oncogenic pathways through integrated approaches and amino acid metabolism in hematologic malignancies.Discover oncology · 2025Review
- Effective in vivo binding energy landscape illustrates kinetic stability of RBPJ-DNA binding.Nature communications · 2025Article
- Nano-strategies for Targeting Tumor-Associated Macrophages in Cancer immunotherapy.Journal of Cancer · 2025Review
- γ-Secretase Inhibitor Potentiates the Activity of Suberoylanilide Hydroxamic Acid by Inhibiting Its Ability to Induce Epithelial to Mesenchymal Transition and Stemness via Notch Pathway Activation in Triple-Negative Breast Cancer Cells.ACS pharmacology & translational science · 2023Article
- OptIC-Notch reveals mechanism that regulates receptor interactions with CSL.Development (Cambridge, England) · 2023Article
- The structure, binding and function of a Notch transcription complex involving RBPJ and the epigenetic reader protein L3MBTL3.Nucleic acids research · 2022Article
- 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
- RITA1 drives the growth of bladder cancer cells by recruiting TRIM25 to facilitate the proteasomal degradation of RBPJ.Cancer science · 2022Article
- α-Phenylalanyl tRNA synthetase competes with Notch signaling through its N-terminal domain.PLoS genetics · 2022Article
- CK1 Is a Druggable Regulator of Microtubule Dynamics and Microtubule-Associated Processes.Cancers · 2022Review
- Colon cancer cells secreted CXCL11 via RBP-Jκ to facilitated tumour-associated macrophage-induced cancer metastasis.Journal of cellular and molecular medicine · 2021Article
- Transcription Factor RBPJL Is Able to Repress Notch Target Gene Expression but Is Non-Responsive to Notch Activation.Cancers · 2021Article
- SUMOylated non-canonical polycomb PRC1.6 complex as a prerequisite for recruitment of transcription factor RBPJ.Epigenetics & chromatin · 2021Article
- Biophysics of Notch Signaling.Annual review of biophysics · 2021Review
- Bioinformatic analysis linking genomic defects to chemosensitivity and mechanism of action.PloS one · 2021Article
- Structurally conserved binding motifs of transcriptional regulators to notch nuclear effector CSL.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- RITA Is Expressed in Trophoblastic Cells and Is Involved in Differentiation Processes of the Placenta.Cells · 2019Article
- CSL controls telomere maintenance and genome stability in human dermal fibroblasts.Nature communications · 2019Article
- The evolution of transcriptional repressors in the Notch signaling pathway: a computational analysis.Hereditas · 2019Article
- The Notch repressor complex in Drosophila: in vivo analysis of Hairless mutants using overexpression experiments.Development genes and evolution · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The Notch pathway is a cell-to-cell signaling mechanism that is essential for tissue development and maintenance, and aberrant Notch signaling has been implicated in various cancers, congenital defects, and cardiovascular diseases. Notch signaling activates the expression of target genes, which are regulated by the transcription factor CSL (CBF1/RBP-J, Su(H), Lag-1). CSL interacts with both transcriptional corepressor and coactivator proteins, functioning as both a repressor and activator, respectively. Although Notch activation complexes are relatively well understood at the structural level, less is known about how CSL interacts with corepressors. Recently, a new RBP-J (mammalian CSL ortholog)-interacting protein termed RITA has been identified and shown to export RBP-J out of the nucleus, thereby leading to the down-regulation of Notch target gene expression. However, the molecular details of RBP-J/RITA interactions are unclear. Here, using a combination of biochemical/cellular, structural, and biophysical techniques, we demonstrate that endogenous RBP-J and RITA proteins interact in cells, map the binding regions necessary for RBP-J·RITA complex formation, and determine the X-ray structure of the RBP-J·RITA complex bound to DNA. To validate the structure and glean more insights into function, we tested structure-based RBP-J and RITA mutants with biochemical/cellular assays and isothermal titration calorimetry. Whereas our structural and biophysical studies demonstrate that RITA binds RBP-J similarly to the RAM (RBP-J-associated molecule) domain of Notch, our biochemical and cellular assays suggest that RITA interacts with additional regions in RBP-J. Taken together, these results provide molecular insights into the mechanism of RITA-mediated regulation of Notch signaling, contributing to our understanding of how CSL functions as a transcriptional repressor of Notch target genes.
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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.