Affinage

RBPJ

Recombining binding protein suppressor of hairless · UniProt Q06330

Length
500 aa
Mass
55.6 kDa
Annotated
2026-06-10
100 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RBPJ (CBF1/RBP-Jκ) is a sequence-specific DNA-binding transcription factor that serves as the central nuclear effector of canonical Notch signaling, recognizing the core GTGGGAA motif and acting as a bistable switch between repression and activation (PMID:8152928, PMID:23651858). In the absence of Notch, RBPJ occupies target enhancers and promoters and recruits corepressor machinery — including CIR linked to histone deacetylase/SAP30 (PMID:9874765), the L3MBTL3–KDM1A/LSD1 module that demethylates H3K4me2 (PMID:29030483), and the SHARP corepressor whose interface with RBPJ is structurally defined and required for repression (PMID:30673607) — and additional polycomb-associated suppressors recruited through the KyoT2/KYOT2 adaptor (RING1, HPC2) (PMID:14999091, PMID:15710417, PMID:35848919). Upon Notch activation, the Notch intracellular domain binds RBPJ through its RAM region and displaces corepressors to assemble an activating complex, derepressing and inducing primary targets such as HES1 to control cell-fate decisions including suppression of myogenesis (PMID:8622698, PMID:9374409, PMID:10066785); ChIP-Seq shows RBPJ occupancy is dynamic, increasing at NICD-co-occupied sites while a separate set of sites remains bound independent of signaling state (PMID:23651858). RBPJ also acts as a Notch-independent transcriptional regulator across tissues: it antagonizes hypoxia-inducible factors to repress angiogenic genes in cardiomyocytes (PMID:27357444), complexes with estrogen receptor α in the uterus (PMID:24971735), represses naive-pluripotency factors during the formative pluripotency transition (PMID:31031137), and binds CDK9/P-TEFb to drive transcriptional elongation in brain tumor-initiating cells (PMID:27322055). In the immune and skeletal systems RBPJ restrains inflammatory osteoclastogenesis and shapes T-cell and macrophage programs by controlling IRF8, IL-23R, NFATc1, and miR-182 (PMID:22610140, PMID:22249448, PMID:27346359, PMID:27183593). RBPJ protein abundance is controlled by cyclin F–mediated SCF polyubiquitylation at Lys315 under metabolic stress, targeting it for proteasomal degradation (PMID:30254149).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1994 High

    Establishing the precise DNA recognition motif of RBPJ was the foundation for defining it as a sequence-specific transcription factor and identifying its genomic targets.

    Evidence EMSA with systematic mutant probes and oligonucleotide selection from random sequences

    PMID:8152928

    Open questions at the time
    • In vitro motif does not establish in vivo occupancy or chromatin context
    • Does not address cofactor requirements for binding
  2. 1994 High

    Identification of Hairless as a direct inhibitor of Su(H)/RBPJ DNA binding revealed that RBPJ activity is negatively regulated by direct protein interactions, foreshadowing antagonist-based control.

    Evidence Purified-protein EMSA, in vitro protein interaction, and reporter assays in Drosophila S2 cells

    PMID:7958912

    Open questions at the time
    • Mechanism in mammalian cells not directly tested
    • No structural basis for inhibition defined
  3. 1996 High

    Demonstrating that the Notch intracellular domain physically binds RBPJ and converts it from repressor to activator established RBPJ as the nuclear effector of Notch signaling.

    Evidence Two-hybrid, co-IP with truncation mapping, and reporter assays in mammalian/human cells

    PMID:8622698 PMID:8643633

    Open questions at the time
    • Did not resolve corepressor identity displaced by NICD
    • Binding-domain mapping but no structure
  4. 1997 High

    Genetic epistasis in an RBP-J null cell line proved Notch transactivation strictly requires RBPJ and separated RAM-mediated binding from IC-mediated transactivation, defining the modular logic of the activator.

    Evidence Deletion mutants and transactivation assays in RBP-J null cells; myogenic differentiation assay

    PMID:9374409

    Open questions at the time
    • Proposed corepressor competition by RAM not directly demonstrated with named corepressor
  5. 1998 High

    Showing RBPJ perturbs basal transcription machinery (TAFII110, TFIIA) provided an early mechanism for active repression independent of chromatin modifiers.

    Evidence Reconstituted in vitro transcription with protein interaction and preinitiation-complex competition assays

    PMID:9620850

    Open questions at the time
    • Relative contribution versus chromatin-based repression unresolved
    • Drosophila TAF homolog; mammalian equivalence not shown here
  6. 1999 High

    Identification of CIR as a corepressor linking RBPJ to HDAC/SAP30 established chromatin-based repression as essential to RBPJ function via loss-of-binding mutants.

    Evidence Interaction assays, co-IP, and reporter repression with CIR-binding-defective RBPJ mutants

    PMID:9874765

    Open questions at the time
    • Genome-wide relevance not assessed
    • Did not exclude additional corepressors
  7. 1999 High

    Ligand-induced Notch signaling was shown to directly and primarily activate HES1 through RBPJ sites, linking the molecular switch to a developmental output (myogenesis block).

    Evidence Delta1 co-culture with cycloheximide controls and constitutively active VP16-RBP-J in C2C12 cells

    PMID:10066785

    Open questions at the time
    • Endogenous chromatin occupancy not directly mapped
  8. 2000 Medium

    SKIP and viral RPMS1 were placed within the RBPJ corepressor complex, showing how viral and cellular factors modulate the repression-to-activation transition.

    Evidence Two-hybrid, GST affinity, co-IP, colocalization, and reporter assays

    PMID:10644367 PMID:11222720

    Open questions at the time
    • Single-lab biochemistry without structural validation
    • Endogenous complex stoichiometry unknown
  9. 2004 Medium

    The RBPJ–KyoT2–RING1 and later HPC2 findings revealed polycomb recruitment to RBPJ via an adaptor, broadening the repressive cofactor repertoire.

    Evidence Two-hybrid, GST pulldown, co-IP, and reporter transactivation with competition

    PMID:14999091 PMID:15710417

    Open questions at the time
    • Indirect (adaptor-mediated) association; no direct RBPJ-RING1 contact
    • Physiological context not defined
  10. 2011 Medium

    Genome-wide ChIP-Seq in leukemia cells showed Notch1 binds preferentially at RBPJ promoter sites and that RBPJ/ZNF143 occupancy is mutually exclusive, introducing competitive site exchange and enhancer-based regulation.

    Evidence ChIP-Seq for Notch1 and RBPJ plus in vitro DNA-binding competition

    PMID:21737748

    Open questions at the time
    • Functional consequence of ZNF143 exchange not established in vivo
    • Enhancer targets correlative
  11. 2013 High

    ChIP-Seq across two Notch states overturned the static-occupancy model, showing RBPJ binding is dynamic at NICD-co-occupied sites yet stable at a Notch-independent subset.

    Evidence ChIP-Seq for RBPJ, NICD, p300, and histone marks under active vs inhibited Notch in myogenic cells

    PMID:23651858

    Open questions at the time
    • Mechanism driving dynamic recruitment unresolved
    • Function of static Notch-independent sites not defined here
  12. 2017 High

    Discovery of the L3MBTL3–KDM1A/LSD1 module recruited by RBPJ defined a conserved enzymatic mechanism (H3K4me2 demethylation) for default repression, with NICD competition for RBPJ as the switch.

    Evidence Proteomics, co-IP, ChIP, demethylation assays, and in vivo genetics in Drosophila and C. elegans

    PMID:29030483

    Open questions at the time
    • Relative contribution versus SHARP/CIR corepressors not quantified
  13. 2017 High

    Crystal structures of RBPJ bound to RITA and (in 2019) SHARP, with structure-based mutants, defined the molecular interfaces underlying repression and the RAM-like binding mode of antagonists.

    Evidence X-ray crystallography, ITC, structure-based mutagenesis, and cellular repression assays

    PMID:28487372 PMID:30673607

    Open questions at the time
    • Structures of full activator (NICD/MAML/RBPJ) on these surfaces not resolved here
    • In vivo relevance of each interface tissue-dependent
  14. 2018 Medium

    Identification of cyclin F–mediated polyubiquitylation at Lys315 established post-translational control of RBPJ abundance under metabolic stress.

    Evidence Ubiquitylation assays, Lys315 mutagenesis, proteasome inhibition, co-IP, and mouse tumor models

    PMID:30254149

    Open questions at the time
    • Single lab; broader physiological triggers of degradation unclear
    • Structural impact of K315 modification unknown
  15. 2022 High

    Multi-omic dissection in mature T cells formally separated Notch-dependent from Notch-independent RBPJ regulation, showing KYOT2/FHL1-mediated repression operates without Notch at a defined gene cluster.

    Evidence RNA-Seq, ChIP-Seq, ATAC-Seq with RBPJ depletion, NICD1 expression, and KYOT2/FHL1 squelching

    PMID:35848919

    Open questions at the time
    • Determinants partitioning sites into Notch-dependent vs independent clusters unresolved
  16. 2016 Medium

    Tissue-specific knockouts revealed broad Notch-independent RBPJ functions — HIF antagonism in cardiomyocytes, CDK9-driven elongation in brain tumor cells, immune/skeletal gene control — expanding RBPJ beyond canonical Notch.

    Evidence Conditional and cell-specific Rbpj knockouts with ChIP, proteomics, and physiological readouts

    PMID:22249448 PMID:22610140 PMID:27183593 PMID:27322055 PMID:27346359 PMID:27357444

    Open questions at the time
    • Each Notch-independent mechanism rests largely on single-lab studies
    • Shared determinant of Notch-independence across tissues not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RBPJ is partitioned between activator, default-repressor, and Notch-independent functions at specific loci, and what cofactor or chromatin features dictate this choice genome-wide, remains unresolved.
  • No unifying model for site-specific activator/repressor/independent assignment
  • Structural basis of the full activation complex on chromatin lacking
  • Quantitative competition between the many corepressors and NICD not reconciled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 3 GO:0060089 molecular transducer activity 2
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1266738 Developmental Biology 3 R-HSA-168256 Immune System 3 R-HSA-4839726 Chromatin organization 2
Partners
CIRESR1KDM1AKYOT2/FHL1L3MBTL3MAML1NOTCH1SHARP
Complex memberships
NICD/MAML/RBPJ Notch activation complexRBPJ-CIR-HDAC/SAP30 corepressor complexRBPJ-KyoT2-RING1 polycomb complexRBPJ-L3MBTL3-KDM1A/LSD1 corepressor complex

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 RBPJ (RBP-Jκ/KBF2) binds the core DNA sequence CGTGGGAA, as determined by electrophoretic mobility shift assay with mutant probes and systematic selection from random oligonucleotide pools; the protein recognizes the GTGGGAA heptanucleotide and makes weaker contacts with flanking ACT and CG sequences. Electrophoretic mobility shift assay (EMSA) with systematic mutant probes; oligonucleotide selection/enrichment from random sequences Nucleic acids research High 8152928
1996 The intracellular domain of mammalian Notch1 (NotchIC) physically interacts with the transcriptional repressor CBF1/RBPJ; the N-terminal 114 amino acids of NotchIC contain the CBF1-binding domain, whereas the ankyrin repeats are dispensable for this interaction. NotchIC is targeted to the transcriptional repression domain (aa 179–361) of CBF1 and transactivates gene expression by abolishing CBF1-mediated repression, the same mechanism used by EBV EBNA2. In vitro binding assay; two-hybrid cotransfection assay; co-immunoprecipitation with truncation mutants; transcriptional reporter assays Molecular and cellular biology High 8622698
1996 Constitutively active human Notch1 (N1ΔEC) physically binds CBF1/RBPJ by co-immunoprecipitation in COS-1 cells and activates transcription through a CBF1-responsive element, demonstrating functional coupling of Notch1 and CBF1 in human cells. Co-immunoprecipitation; transcriptional reporter assay (CAT) in multiple cell lines Proceedings of the National Academy of Sciences of the United States of America High 8643633
1997 Notch1 intracellular region (RAMIC) contains two separable functional domains: RAM (sufficient for RBP-J binding) and IC (transactivation domain with weaker RBP-J interaction). Transactivation by IC requires RBP-J, demonstrated using an RBP-J null cell line. The RAM domain synergistically stimulates IC transactivation, proposed to compete with a putative co-repressor for RBP-J binding. Suppression of myogenic differentiation by Notch1 correlates with RBP-J–dependent transactivation. Deletion mutant analysis; transactivation assay in RBP-J null cell line; myogenic differentiation assay with RBP-J-VP16 fusion Development (Cambridge, England) High 9374409
1999 CBF1/RBPJ mediates transcriptional repression by binding a unique corepressor CIR, which in turn binds histone deacetylase and SAP30, linking CBF1 to the histone deacetylase complex. Two CBF1 mutants unable to bind CIR lose repressor function, establishing CIR recruitment as essential for CBF1-mediated repression. Protein-protein interaction assays; co-immunoprecipitation; reporter repression assays; CBF1 mutants defective in CIR binding Proceedings of the National Academy of Sciences of the United States of America High 9874765
1999 Delta1-induced Notch signaling activates transcription of RBP-J–binding motif-containing promoters including HES1, and this activation is primary (cycloheximide-insensitive). HES1 induction subsequently represses MyoD mRNA, blocking myogenic differentiation. A constitutively active VP16-RBP-J fusion recapitulates Notch-mediated inhibition of myogenesis. Co-culture with Delta1-expressing cells; cycloheximide treatment; mRNA expression analysis; VP16-RBP-J transfection in C2C12 cells The Journal of biological chemistry High 10066785
1998 RBP-J represses transcription by directly interacting with two transcriptional coactivators, dTAFII110 (a TFIID subunit) and TFIIA, perturbing their optimal interactions. RBP-J does not occlude other transcription factor binding to promoters. The RBP-J interaction domain on dTAFII110 overlaps with the TFIIA-interaction domain but is distinct from the Sp1-interaction domain. In vitro transcription assay; protein-protein interaction assays; pre-formed transcription preinitiation complex competition experiments Genes & development High 9620850
1994 The Drosophila Hairless protein directly inhibits DNA binding of both Su(H) and its human homolog KBF2/RBP-Jκ through protein-protein interactions in vitro. This inhibitory interaction is consistent with Su(H)-driven transcriptional activation being suppressed by Hairless in Drosophila S2 cells, placing Hairless as a negative regulator of Su(H)/RBPJ activity. Protein purification; EMSA; in vitro protein-protein interaction; transcriptional reporter assay in Drosophila S2 cells Genes & development High 7958912
2000 SKIP interacts with the CBF1 corepressor complex components (SMRT, CIR, Sin3A, HDAC2) and also with EBNA2, and is required for efficient EBNA2-mediated activation of CBF1-dependent promoters. EBNA2 competes with the SMRT-corepressor complex for contacts on SKIP and CBF1 to relieve repression. Yeast two-hybrid screen; GST affinity assays; mammalian two-hybrid assays; immunofluorescence co-localization; transcriptional reporter assays Journal of virology Medium 10644367
2001 EBV RPMS1 protein interacts with both CBF1/RBPJ and components of the CBF1-associated corepressor complex (Sin3A, CIR), and negatively regulates EBNA2- and NotchIC-mediated transcriptional activation by blocking relief of CBF1-mediated repression and interfering with SKIP-CIR interactions. GST affinity assays; co-immunoprecipitation; mammalian two-hybrid; immunofluorescence co-localization; reporter assays; muscle differentiation assay Journal of virology Medium 11222720
2003 CBF1/RBPJ binds to the κB site of the IκBα promoter and represses IκBα transcription, thereby elevating basal NF-κB activity. The Notch1 intracellular domain (NICD) relieves this CBF1-mediated repression of IκBα in an RAM-domain-dependent manner, and co-activation with p300 enhances IκBα promoter function. EMSA; promoter mutagenesis; CBF1 overexpression in COS1 cells; NICD co-transfection; IκBα protein level measurement The Journal of biological chemistry Medium 12700242
2004 The polycomb group protein RING1 is recruited to RBP-J through the LIM protein KyoT2, forming a three-molecule RBP-J–KyoT2–RING1 complex. RING1 and RBP-J do not associate directly. Overexpression of RING1 together with KyoT2 inhibits NIC-mediated transactivation of RBP-J, and this suppression is abrogated by competing KyoT2 away from RING1. Yeast two-hybrid; GST pulldown; co-immunoprecipitation; reporter transactivation assays Nucleic acids research Medium 14999091
2005 The PcG protein HPC2 interacts with KyoT2 LIM domains and, when overexpressed, inhibits NIC-mediated transactivation of RBP-J-dependent promoters as well as transactivation by constitutively active RBP-J-VP16, establishing HPC2 as an additional co-suppressor recruited to RBP-J via KyoT2. Yeast two-hybrid; GST pulldown; co-immunoprecipitation; mammalian two-hybrid; reporter assays FEBS letters Medium 15710417
2011 In zebrafish, Wt1a, Foxc1a, and Rbpj physically interact with each other by GST pulldown and co-immunoprecipitation; only Rbpj binds the Notch intracellular domain (NICD). In transactivation assays, combinations of Wt1, FoxC1/2, and NICD synergistically activate the Hey1 promoter, demonstrating that these factors converge on common target genes as a physical complex to regulate podocyte fate. GST pulldown; co-immunoprecipitation; transactivation reporter assays; morpholino knockdown in zebrafish Developmental biology Medium 21871448
2013 ChIP-Seq in myogenic cells demonstrates that RBPJ binding is dynamic: at sites co-occupied by NICD, RBPJ binding increases upon Notch activation, contradicting a static occupancy model. A distinct subset of RBPJ sites shows static binding irrespective of Notch activity and lacks NICD or p300 co-occupancy, indicating RBPJ can occupy chromatin independently of Notch signaling state. ChIP-Seq for RBPJ, NICD, p300, H3K4me3, H3K4me1, H3K27ac under active vs. inhibitory Notch conditions Genes & development High 23651858
2017 RBPJ recruits L3MBTL3 (MBT1) and the histone demethylase KDM1A/LSD1 to enhancers of Notch target genes in the absence of NICD, leading to H3K4me2 demethylation and transcriptional repression. L3MBTL3 competes with NICD for binding to RBPJ. This mechanism is evolutionarily conserved in Drosophila and C. elegans. Proteomic/mass spectrometry identification of RBPJ interactors; co-immunoprecipitation; ChIP; H3K4me2 demethylation assays; in vivo genetic analyses in Drosophila and C. elegans The EMBO journal High 29030483
2019 The crystal structure of RBPJ bound to the corepressor SHARP and DNA was determined, revealing SHARP's mode of binding to RBPJ. Structure-based mutants of RBPJ that are deficient for SHARP binding are incapable of repressing Notch-responsive gene expression in cells, demonstrating that the RBPJ–SHARP interface is essential for RBPJ's repressor function. X-ray crystallography; biophysical binding assays; structure-based mutagenesis; cellular transcriptional repression assays Cell reports High 30673607
2017 The X-ray structure of RBPJ bound to RITA and DNA was determined, showing RITA binds RBPJ similarly to the RAM domain of Notch. Structure-based mutants and ITC measurements mapped binding regions; biochemical/cellular assays showed RITA interacts with additional regions beyond the RAM-like interface. RITA-mediated down-regulation of Notch target genes requires RBP-J/RITA complex formation. X-ray crystallography; isothermal titration calorimetry; biochemical binding assays; cellular reporter assays; endogenous co-immunoprecipitation The Journal of biological chemistry High 28487372
2018 Cyclin F (an SCF E3 ubiquitin ligase substrate-recognition subunit) mediates polyubiquitylation of RBPJ at Lys315 under metabolic stress, leading to proteasomal degradation of RBPJ. This degradation is induced in a FOXO1-dependent manner and attenuates RBPJ-dependent IDH1 expression. Ubiquitylation assays; site-directed mutagenesis (Lys315); proteasome inhibitor experiments; co-immunoprecipitation; mouse tumor models Cancer research Medium 30254149
2016 RBPJ maintains brain tumor-initiating cells (BTICs) by binding CDK9 (a component of P-TEFb) at target gene promoters to enhance transcriptional elongation. MYC binds the RBPJ promoter and drives RBPJ expression in BTICs. This RBPJ function is distinct from canonical Notch signaling. Proteomics (RBPJ interactome); ChIP; shRNA knockdown; tumor growth assays; BET bromodomain inhibitor treatment The Journal of clinical investigation Medium 27322055
2019 RBPJ-Inhibitor-1 (RIN1), a small molecule, disrupts the interaction between NOTCH ICD and RBPJ, and also blocks the functional interaction of RBPJ with SHARP, inhibiting both the activating (NOTCH-bound) and repressing (SHARP-bound) complexes of RBPJ. Gene expression changes induced by RIN1 resemble siRNA silencing of RBPJ. Small-molecule screen; protein-protein interaction assays; gene expression profiling; cell proliferation assays; C2C12 differentiation assay Scientific reports Medium 31346210
2014 Uterine RBPJ interacts physically with estrogen receptor α (ERα) in a Notch pathway-independent manner to regulate uterine lumen shape transformation prior to embryo attachment. At post-implantation stages, RBPJ directly regulates uterine matrix metalloproteinase expression in a Notch pathway-dependent manner for decidual remodeling. Conditional knockout mice (uterine-specific Rbpj deletion); co-immunoprecipitation (RBPJ–ERα); gene expression analysis; embryo transfer experiments Cell research Medium 24971735
2012 Notch-RBP-J signaling controls expression of the transcription factor IRF8 by selectively augmenting IRAK2-dependent TLR4 signaling to kinase MNK1 and downstream eIF4E-mediated translational control, thereby regulating IRF8 protein synthesis and M1 macrophage polarization. Myeloid-specific RBP-J conditional knockout; IRF8 protein/mRNA analysis; signaling pathway inhibition (IRAK2, MNK1, eIF4E); Listeria infection model Nature immunology Medium 22610140
2012 RBP-J suppresses TNF-induced osteoclastogenesis by attenuating c-Fos activation and suppressing BLIMP1 induction, thereby preventing downregulation of the transcriptional repressor IRF-8, which blocks osteoclast differentiation. Myeloid-specific RBP-J deletion converted TNF into a potent RANK-independent osteoclastogenic factor. Myeloid-specific conditional Rbpj knockout; RANK-deficient mouse model; reporter assays for c-Fos and NFATc1; in vivo inflammatory bone resorption model The Journal of experimental medicine High 22249448
2014 RBP-J suppresses ITAM-mediated costimulation of osteoclastogenesis by inhibiting PLCγ2 expression and function and downstream calcium-CaMKK/PYK2 signaling. RBP-J also suppresses PLCγ2 expression indirectly via a TGF-β/PLCγ2/calcium axis. Deletion of Rbpj in DAP12-deficient mice substantially rescued defects in bone remodeling. Conditional Rbpj knockout; double KO with DAP12 deficiency; calcium oscillation measurement; PLCγ2 expression and phosphorylation assays; TGF-β pathway analysis The Journal of clinical investigation Medium 25329696
2012 Notch-RBPjk signaling suppresses osteoblast differentiation in part through Hey1-mediated inhibition of NFATc1: deletion of RBPjk increases NFATc1 expression, and Hey1 binds to and suppresses the NFATc1 promoter. Pharmacological inhibition of NFAT alleviated the high-bone-mass phenotype of RBPjk-deleted mice. Conditional Rbpjk knockout; Hey1/HeyL double knockout; ChIP (Hey1 at NFATc1 promoter); NFAT pharmacological inhibition in vivo PLoS genetics Medium 22457635
2013 The RBPJ/NICD transcriptional complex is recruited to Rbpj-binding sites upstream of the Sox9 promoter, associated with transcriptional repression of Sox9, as demonstrated by ChIP in a chondrocyte differentiation cellular model. Deletion of Rbpj on a Notch gain-of-function background restores Sox9 protein levels, demonstrating Rbpj-dependent regulation of Sox9. Chromatin immunoprecipitation (ChIP); genetic rescue (Rbpj deletion on Notch GOF background); Sox9 protein expression analysis Journal of bone and mineral research Medium 22991339
2016 RBPJ binds and trans-activates the Il23r promoter in Th17 cells to drive IL-23R expression, while repressing IL-10 production. In the absence of RBPJ, Th17 cells fail to upregulate IL-23R and do not induce autoimmune tissue inflammation; overexpression of IL-23R rescues pathogenicity of RBPJ-deficient Th17 cells. Conditional Rbpj knockout in T cells; ChIP (RBPJ at Il23r promoter); IL-23R overexpression rescue; in vivo autoimmune model Cell reports Medium 27346359
2016 RBP-J suppresses TNF-α-induced osteoclastogenesis by repressing miR-182 expression through binding to specific open chromatin regions in the miR-182 promoter. miR-182 promotes osteoclastogenesis by inhibiting Foxo3 and Maml1; suppression of miR-182 by RBP-J is a critical mechanism restraining TNF-induced osteoclast differentiation. High-throughput miRNA sequencing; ChIP (RBP-J at miR-182 promoter); gain/loss-of-function of miR-182; target validation (Foxo3, Maml1) Journal of immunology Medium 27183593
2016 In cardiomyocytes, RBPJ acts as a Notch-independent repressor of multiple pro-angiogenic and angiostatic factor genes by antagonizing hypoxia-inducible factors (HIFs). Cardiomyocyte-specific Rbpj deletion increased cardiac microvascularization and improved heart function after myocardial infarction. Cardiomyocyte-specific conditional Rbpj knockout; gene expression profiling; hypoxia/HIF pathway analysis; echocardiography and cardiac function assessment post-MI Nature communications Medium 27357444
2020 YY1 binds the N-terminal domain of RBPJ and competes with Notch coactivator MAML1 for RBPJ binding, thereby impairing NICD/MAML1/RBPJ ternary complex formation and functioning as a repressor of Notch signaling in endothelial cells to control tip-stalk cell fate during sprouting angiogenesis. Co-immunoprecipitation; domain mapping; endothelial EC-specific YY1 knockout; retinal sprouting assay; aortic ring assay Proceedings of the National Academy of Sciences of the United States of America Medium 32075915
2019 RBPJ represses naive-pluripotency factors TBX3 and NANOG to secure exit from the naive state during formative pluripotency transition in mouse ESCs, acting independently of ETV5 and TCF3. Triple deletion of Etv5, Rbpj, and Tcf3 locks ESCs in self-renewal even under differentiation stimuli. Genetic triple knockout (Etv5, Rbpj, Tcf3) in mouse ESCs; gene expression profiling; genome-wide binding analysis Cell stem cell Medium 31031137
2022 In mature T-cells lacking active Notch signaling, RBPJ functions as a repressor at Notch target genes in a Notch-independent manner through corepressor KYOT2/FHL1. Depletion of RBPJ or squelching of KYOT2/FHL1 both lead to upregulation of Notch target genes. ChIP-Seq and ATAC-seq defined four clusters of RBPJ-regulated genes, some Notch-dependent and some Notch-independent. RBPJ depletion in mature T-cells; RNA-Seq; ChIP-Seq; ATAC-Seq; NICD1 ectopic expression; KYOT2/FHL1 squelching Nucleic acids research High 35848919
2011 ChIP-Seq in human and murine T-lymphoblastic leukemia cells reveals that Notch1 binds preferentially to RBPJ binding sites in promoters, and that RBPJ and ZNF143 binding to DNA is mutually exclusive in vitro, suggesting exchange of RBPJ/Notch1 and ZNF143 complexes at shared sites in cells. Many direct Notch1 target genes lack promoter binding and are regulated by enhancers identified near MYC, DTX1, IGF1R, IL7R, and the GIMAP cluster. ChIP-Seq for Notch1 and RBPJ; in vitro DNA binding competition assays; identification of enhancers Proceedings of the National Academy of Sciences of the United States of America Medium 21737748
2014 Loss of RBPJ in human cancer cell lines derepresses target gene promoters, allowing Notch-independent activation by alternate transcription factors NF-κB and MYC, which are essential for survival of RBPJ-depleted cells. Global H4ac profiling confirmed widespread transcriptional dysregulation of the cell death pathway. RBPJ depletion in human cancer cell lines; xenograft tumor growth assays; H4ac ChIP-Seq; NF-κB and MYC functional studies The Journal of experimental medicine Medium 25512468
1999 CBF1/RBPJ binds to the κB site of the IL-6 gene promoter in cell lines of diverse origin, acts as a negative regulator of IL-6 gene transcription upon overexpression, and induces DNA bending at the recognition site, suggesting CBF1 can influence transcription by imposing specific promoter conformation. EMSA; transfection reporter assays in HeLa cells; DNA bending assay Nucleic acids research Low 10373597
2016 Endothelial Jagged1-RBPJ signaling promotes NF-κB-dependent transcription: the Notch1 intracellular domain (N1ICD) physically interacts with NF-κB in the nucleus, and this N1ICD-NF-κB interaction is required for reciprocal transactivation of target genes including VCAM-1 in atherosclerosis. Endothelial-specific Rbpj conditional knockout; transcriptome analysis; nuclear co-IP (N1ICD and NF-κB); intravital microscopy Cardiovascular research Medium 27496872

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Notch-RBP-J signaling controls the homeostasis of CD8- dendritic cells in the spleen. The Journal of experimental medicine 723 17591855
2002 Notch-RBP-J signaling is involved in cell fate determination of marginal zone B cells. Nature immunology 399 11967543
1996 Truncated mammalian Notch1 activates CBF1/RBPJk-repressed genes by a mechanism resembling that of Epstein-Barr virus EBNA2. Molecular and cellular biology 393 8622698
2012 Notch-RBP-J signaling regulates the transcription factor IRF8 to promote inflammatory macrophage polarization. Nature immunology 367 22610140
1996 Notch signaling inhibits muscle cell differentiation through a CBF1-independent pathway. Development (Cambridge, England) 332 9012498
1990 Yeast centromere binding protein CBF1, of the helix-loop-helix protein family, is required for chromosome stability and methionine prototrophy. Cell 311 2185892
1997 Involvement of RBP-J in biological functions of mouse Notch1 and its derivatives. Development (Cambridge, England) 262 9374409
1994 Recognition sequence of a highly conserved DNA binding protein RBP-J kappa. Nucleic acids research 248 8152928
1999 CIR, a corepressor linking the DNA binding factor CBF1 to the histone deacetylase complex. Proceedings of the National Academy of Sciences of the United States of America 246 9874765
1999 Delta-induced Notch signaling mediated by RBP-J inhibits MyoD expression and myogenesis. The Journal of biological chemistry 227 10066785
2013 Dynamic binding of RBPJ is determined by Notch signaling status. Genes & development 210 23651858
2011 Genome-wide analysis reveals conserved and divergent features of Notch1/RBPJ binding in human and murine T-lymphoblastic leukemia cells. Proceedings of the National Academy of Sciences of the United States of America 208 21737748
1994 Inhibition of the DNA-binding activity of Drosophila suppressor of hairless and of its human homolog, KBF2/RBP-J kappa, by direct protein-protein interaction with Drosophila hairless. Genes & development 162 7958912
2012 TNF-induced osteoclastogenesis and inflammatory bone resorption are inhibited by transcription factor RBP-J. The Journal of experimental medicine 150 22249448
2006 The CBF1-dependent low temperature signalling pathway, regulon and increase in freeze tolerance are conserved in Populus spp. Plant, cell & environment 132 17080948
2005 Inhibition of Notch/RBP-J signaling induces hair cell formation in neonate mouse cochleas. Journal of molecular medicine (Berlin, Germany) 132 16283144
2006 The canonical Notch/RBP-J signaling pathway controls the balance of cell lineages in mammary epithelium during pregnancy. Developmental biology 114 16581056
2000 Notch signalling via RBP-J promotes myeloid differentiation. The EMBO journal 108 10835354
1997 Epstein-Barr virus immortalization: Notch2 interacts with CBF1 and blocks differentiation. Journal of virology 99 9032325
2016 RBPJ Controls Development of Pathogenic Th17 Cells by Regulating IL-23 Receptor Expression. Cell reports 98 27346359
2000 A role for SKIP in EBNA2 activation of CBF1-repressed promoters. Journal of virology 97 10644367
2005 Notch-mediated CBF-1/RBP-J{kappa}-dependent regulation of human vascular smooth muscle cell phenotype in vitro. American journal of physiology. Cell physiology 96 15987768
2006 Notch/Rbp-j signaling prevents premature endocrine and ductal cell differentiation in the pancreas. Cell metabolism 92 16399505
2009 Rbpj cell autonomous regulation of retinal ganglion cell and cone photoreceptor fates in the mouse retina. The Journal of neuroscience : the official journal of the Society for Neuroscience 86 19828801
2019 Complementary Activity of ETV5, RBPJ, and TCF3 Drives Formative Transition from Naive Pluripotency. Cell stem cell 85 31031137
1997 Assembly of a bZIP-bHLH transcription activation complex: formation of the yeast Cbf1-Met4-Met28 complex is regulated through Met28 stimulation of Cbf1 DNA binding. The EMBO journal 84 9171357
1997 Both Epstein-Barr viral nuclear antigen 2 (EBNA2) and activated Notch1 transactivate genes by interacting with the cellular protein RBP-J kappa. Immunobiology 81 9442401
2012 Physiological notch signaling maintains bone homeostasis via RBPjk and Hey upstream of NFATc1. PLoS genetics 80 22457635
2003 Basal expression of IkappaBalpha is controlled by the mammalian transcriptional repressor RBP-J (CBF1) and its activator Notch1. The Journal of biological chemistry 76 12700242
2011 Diet-induced aortic valve disease in mice haploinsufficient for the Notch pathway effector RBPJK/CSL. Arteriosclerosis, thrombosis, and vascular biology 75 21493891
1998 The mammalian transcriptional repressor RBP (CBF1) targets TFIID and TFIIA to prevent activated transcription. Genes & development 74 9620850
2019 RBPJ-dependent Notch signaling initiates the T cell program in a subset of thymus-seeding progenitors. Nature immunology 73 31636466
2014 Uterine Rbpj is required for embryonic-uterine orientation and decidual remodeling via Notch pathway-independent and -dependent mechanisms. Cell research 73 24971735
1996 Constitutively active human Notch1 binds to the transcription factor CBF1 and stimulates transcription through a promoter containing a CBF1-responsive element. Proceedings of the National Academy of Sciences of the United States of America 73 8643633
2011 Wt1a, Foxc1a, and the Notch mediator Rbpj physically interact and regulate the formation of podocytes in zebrafish. Developmental biology 72 21871448
1995 Contribution of conserved amino acids in mediating the interaction between EBNA2 and CBF1/RBPJk. Journal of virology 71 7853539
2010 Two opposing roles of RBP-J in Notch signaling. Current topics in developmental biology 64 20816397
2008 Melanoblasts' proper location and timed differentiation depend on Notch/RBP-J signaling in postnatal hair follicles. The Journal of investigative dermatology 64 18463680
2019 Loss of the transcription factor RBPJ induces disease-promoting properties in brain pericytes. Nature communications 63 31249304
2022 Exosomal hsa_circ_0004658 derived from RBPJ overexpressed-macrophages inhibits hepatocellular carcinoma progression via miR-499b-5p/JAM3. Cell death & disease 61 35013102
2016 RBP-J-Regulated miR-182 Promotes TNF-α-Induced Osteoclastogenesis. Journal of immunology (Baltimore, Md. : 1950) 61 27183593
2011 Transcriptional regulator RBP-J regulates the number and plasticity of renin cells. Physiological genomics 61 21750232
2020 A circular RNA derived from DAB1 promotes cell proliferation and osteogenic differentiation of BMSCs via RBPJ/DAB1 axis. Cell death & disease 60 32415085
2017 RBPJ/CBF1 interacts with L3MBTL3/MBT1 to promote repression of Notch signaling via histone demethylase KDM1A/LSD1. The EMBO journal 60 29030483
2011 Rbpj regulates development of prosensory cells in the mammalian inner ear. Developmental biology 60 21420948
2013 Notch gain of function inhibits chondrocyte differentiation via Rbpj-dependent suppression of Sox9. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 59 22991339
1993 Human Jk recombination signal binding protein gene (IGKJRB): comparison with its mouse homologue. Genomics 58 8406481
2016 RBPJ maintains brain tumor-initiating cells through CDK9-mediated transcriptional elongation. The Journal of clinical investigation 57 27322055
2001 Epstein-Barr virus BamHi-a rightward transcript-encoded RPMS protein interacts with the CBF1-associated corepressor CIR to negatively regulate the activity of EBNA2 and NotchIC. Journal of virology 56 11222720
2004 RING1 inhibits transactivation of RBP-J by Notch through interaction with LIM protein KyoT2. Nucleic acids research 55 14999091
2021 Sox9 and Rbpj differentially regulate endothelial to mesenchymal transition and wound scarring in murine endovascular progenitors. Nature communications 54 33963183
2014 Loss of the Notch effector RBPJ promotes tumorigenesis. The Journal of experimental medicine 52 25512468
2019 Rbpj expression in regulatory T cells is critical for restraining TH2 responses. Nature communications 51 30962454
2014 RBP-J imposes a requirement for ITAM-mediated costimulation of osteoclastogenesis. The Journal of clinical investigation 51 25329696
2016 Endothelial Jag1-RBPJ signalling promotes inflammatory leucocyte recruitment and atherosclerosis. Cardiovascular research 50 27496872
2014 Deletion of Rbpj from postnatal endothelium leads to abnormal arteriovenous shunting in mice. Development (Cambridge, England) 50 25209249
2019 Disruption of NOTCH signaling by a small molecule inhibitor of the transcription factor RBPJ. Scientific reports 48 31346210
2007 The CBF1-independent Notch1 signal pathway activates human c-myc expression partially via transcription factor YY1. Carcinogenesis 48 17434929
2008 Notch signaling regulates the FOXP3 promoter through RBP-J- and Hes1-dependent mechanisms. Molecular and cellular biochemistry 46 18777163
2018 Long non-coding RNA AFAP1-AS1/miR-320a/RBPJ axis regulates laryngeal carcinoma cell stemness and chemoresistance. Journal of cellular and molecular medicine 45 29971915
2020 Merkel cell carcinoma-derived exosome-shuttle miR-375 induces fibroblast polarization by inhibition of RBPJ and p53. Oncogene 43 33311552
2016 Notch-independent RBPJ controls angiogenesis in the adult heart. Nature communications 43 27357444
2022 Exosomal circRNA BTG2 derived from RBP-J overexpressed-macrophages inhibits glioma progression via miR-25-3p/PTEN. Cell death & disease 41 35643814
2011 EBV nuclear antigen EBNALP dismisses transcription repressors NCoR and RBPJ from enhancers and EBNA2 increases NCoR-deficient RBPJ DNA binding. Proceedings of the National Academy of Sciences of the United States of America 41 21518914
2019 Structural and Functional Studies of the RBPJ-SHARP Complex Reveal a Conserved Corepressor Binding Site. Cell reports 40 30673607
2000 Interaction of yeast kinetochore proteins with centromere-protein/transcription factor Cbf1. Proceedings of the National Academy of Sciences of the United States of America 39 11070082
1992 Genomic organization of mouse J kappa recombination signal binding protein (RBP-J kappa) gene. The Journal of biological chemistry 39 1740450
2005 Epstein-Barr virus nuclear protein 3A domains essential for growth of lymphoblasts: transcriptional regulation through RBP-Jkappa/CBF1 is critical. Journal of virology 38 16051810
2003 Regulation of B cell development by Notch/RBP-J signaling. Seminars in immunology 37 12681948
2021 Transcription Factor RBPJ as a Molecular Switch in Regulating the Notch Response. Advances in experimental medicine and biology 36 33034023
1999 Interaction of the nuclear protein CBF1 with the kappaB site of the IL-6 gene promoter. Nucleic acids research 32 10373597
2005 A somatic knockout of CBF1 in a human B-cell line reveals that induction of CD21 and CCR7 by EBNA-2 is strictly CBF1 dependent and that downregulation of immunoglobulin M is partially CBF1 independent. Journal of virology 31 15994772
2017 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 30 28487372
2016 The Indeterminate Domain Protein ROC1 Regulates Chilling Tolerance via Activation of DREB1B/CBF1 in Rice. International journal of molecular sciences 30 26927068
2011 Ptf1a/Rbpj complex inhibits ganglion cell fate and drives the specification of all horizontal cell subtypes in the chick retina. Developmental biology 30 21839069
2022 Notch-dependent and -independent functions of transcription factor RBPJ. Nucleic acids research 29 35848919
2021 LncRNA FTX Promotes Colorectal Cancer Cells Migration and Invasion by miRNA-590-5p/RBPJ Axis. Biochemical genetics 29 33389283
2016 An Intronic Flk1 Enhancer Directs Arterial-Specific Expression via RBPJ-Mediated Venous Repression. Arteriosclerosis, thrombosis, and vascular biology 29 27079877
2012 Requirements for Jag1-Rbpj mediated Notch signaling during early mouse lens development. Developmental dynamics : an official publication of the American Association of Anatomists 29 22275127
2021 Ageing promotes early T follicular helper cell differentiation by modulating expression of RBPJ. Aging cell 28 33387451
2020 RBPJ contributes to the malignancy of glioblastoma and induction of proneural-mesenchymal transition via IL-6-STAT3 pathway. Cancer science 28 32885530
2018 Cyclin F-Dependent Degradation of RBPJ Inhibits IDH1R132H-Mediated Tumorigenesis. Cancer research 28 30254149
2016 EBNA3C Directs Recruitment of RBPJ (CBF1) to Chromatin during the Process of Gene Repression in EBV Infected B Cells. PLoS pathogens 26 26751214
2001 Activation of the Notch-regulated transcription factor CBF1/RBP-Jkappa through the 13SE1A oncoprotein. Genes & development 26 11230145
2018 RBPJ mediates uterine repair in the mouse and is reduced in women with recurrent pregnancy loss. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 25 29242273
2013 Abortive lytic reactivation of KSHV in CBF1/CSL deficient human B cell lines. PLoS pathogens 25 23696732
2005 The PcG protein HPC2 inhibits RBP-J-mediated transcription by interacting with LIM protein KyoT2. FEBS letters 25 15710417
2015 RBPJ inhibition impairs the growth of lung cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 24 25589461
2008 A dominant suppressor mutation of the met30 cell cycle defect suggests regulation of the Saccharomyces cerevisiae Met4-Cbf1 transcription complex by Met32. The Journal of biological chemistry 24 18308733
2009 RBP-J promotes neuronal differentiation and inhibits oligodendroglial development in adult neurogenesis. Developmental biology 23 19501584
2006 Epstein-Barr virus nuclear antigen 2 trans-activates the cellular antiapoptotic bfl-1 gene by a CBF1/RBPJ kappa-dependent pathway. Journal of virology 23 16873269
2023 A C2H2-type zinc finger protein ZAT12 of Poncirus trifoliata acts downstream of CBF1 to regulate cold tolerance. The Plant journal : for cell and molecular biology 22 38017362
2015 The canonical Notch pathway effector RBP-J regulates neuronal plasticity and expression of GABA transporters in hippocampal networks. Hippocampus 22 25515406
2020 Endothelial-specific YY1 governs sprouting angiogenesis through directly interacting with RBPJ. Proceedings of the National Academy of Sciences of the United States of America 21 32075915
2006 Epstein-Barr virus nuclear antigen 2 induces FcRH5 expression through CBF1. Blood 21 16439682
2011 The role of the transcription factor Rbpj in the development of dorsal root ganglia. Neural development 20 21510873
2016 The Notch Intracellular Domain Has an RBPj-Independent Role during Mouse Hair Follicular Development. The Journal of investigative dermatology 19 26940862
2019 Regulatory network mediated by RBP-J/NFATc1-miR182 controls inflammatory bone resorption. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 18 31908034
2018 Blockade of RBP-J-Mediated Notch Signaling Pathway Exacerbates Cardiac Remodeling after Infarction by Increasing Apoptosis in Mice. BioMed research international 18 30065940
2022 Endothelial RBPJ Is Essential for the Education of Tumor-Associated Macrophages. Cancer research 17 36200806

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