Affinage

RREB1

Ras-responsive element-binding protein 1 · UniProt Q92766

Length
1687 aa
Mass
181.4 kDa
Annotated
2026-06-10
64 papers in source corpus 28 papers cited in narrative 29 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

RREB1 (Ras-responsive element binding protein 1) is a multi-zinc-finger transcription factor that serves as a downstream effector of RAS/MAPK signaling, binding Ras-responsive elements (RREs; consensus CCCCAAACCACCCC) to control gene programs governing epithelial cell behavior, development, and neuronal maintenance (PMID:8816445, PMID:24418439). It acts bidirectionally: as an activator it transactivates promoters including calcitonin, p53, ZIP3, AKT1, and others (PMID:8816445, PMID:19558368, PMID:25050557, PMID:34419497), and as a repressor it silences targets such as HLA-G, hZIP1, and miR-143/145 through interaction with the CtBP co-repressor complex and chromatin-remodeling/histone-deacetylase machinery (PMID:19890057, PMID:19802870, PMID:22751122). A central role is the coordination of EMT: RREB1 physically recruits TGF-β/Nodal-activated SMAD transcription factors to the SNAIL promoter to drive both carcinoma fibrogenic EMT and developmental EMT during gastrulation, and its loss in mouse embryos perturbs F-actin and adherens-junction organization, causing aberrant epithelial cell exit reminiscent of metastasis (PMID:31915377, PMID:33929320). RREB1 also recruits a Sin3a–KDM1A complex to MAPK pathway gene promoters to set H3K4 methylation, and Rreb1 haploinsufficiency in mice epigenetically derepresses RAS-MAPK targets and phenocopies Noonan syndrome features such as hypertelorism and cardiac hypertrophy (PMID:32938917). In the nervous system, RREB1/orthologs act as negative regulators of RAS/MAPK target genes required for axonal integrity and neuronal survival, with loss causing Purkinje cell degeneration, defective autophagy, and accumulation of P62/ubiquitin inclusions (PMID:38198538, PMID:29295933). Functional conservation is demonstrated by human RREB1 rescuing Drosophila Hindsight/Pebbled mutant phenotypes (PMID:24418439, PMID:29295933).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1996 High

    Established the founding molecular identity of RREB1 as a zinc-finger transcription factor that binds the Ras-responsive element and couples RAS/RAF signaling to target gene transactivation.

    Evidence cDNA cloning, DNase I footprinting, and reporter transactivation in medullary thyroid cancer cells

    PMID:8816445

    Open questions at the time
    • Did not define the full repertoire of target genes
    • No structure of the DNA-binding zinc fingers
    • Mechanism of RAS-dependent activation not resolved
  2. 2008 High

    Linked RREB1 to a cellular phenotype — collective epithelial cell migration via modulation of cell-cell adhesion — connecting its transcriptional role to morphogenetic behavior.

    Evidence siRNA knockdown and scratch-wound/live-imaging in MCF10A cells with orthologous Drosophila hnt genetics

    PMID:18394891

    Open questions at the time
    • Adhesion target genes not identified
    • Did not connect phenotype to specific promoters
  3. 2009 Medium

    Defined RREB1's dual activator/repressor mode: it represses HLA-G via the CtBP co-repressor complex while activating p53 under genotoxic stress to control apoptosis.

    Evidence Promoter pull-down/MS, Co-IP with CtBP subunits, ChIP and reporter assays in human cells

    PMID:19558368 PMID:19890057

    Open questions at the time
    • Single-lab findings
    • Determinants of activator-vs-repressor switching not defined
    • CtBP recruitment mechanism not mapped at residue level
  4. 2010 High

    Demonstrated direct, mutation-sensitive promoter binding underlying repression of the zinc transporter hZIP1 in prostate cancer, establishing RREB1 as a regulator of cellular zinc handling.

    Evidence EMSA, ChIP, site-directed mutagenesis, and reporter/overexpression-knockdown in prostate cancer cells

    PMID:19802870 PMID:21360563

    Open questions at the time
    • Co-repressor for hZIP1 silencing not defined
    • Physiological consequence of zinc dysregulation in vivo untested
  5. 2012 Medium

    Positioned RREB1 within a RAS feedback circuit by showing it is MAPK-activated and represses miR-143/145, which in turn target KRAS and RREB1.

    Evidence ChIP, reporter assays, and MAPK pathway inhibition in cancer cells

    PMID:22751122

    Open questions at the time
    • Single lab
    • Repressive chromatin machinery at miR-143/145 not detailed
  6. 2013 Medium

    Identified co-activators and additional target genes (DJ-1 cooperation at the CCK promoter; positive regulation of ZIP3), broadening the activator repertoire and demonstrating in vivo relevance.

    Evidence Co-IP, reporter/promoter binding, and DJ-1-knockout mouse serum CCK; ZIP3/zinc assays in pancreatic cells

    PMID:24348900 PMID:25050557

    Open questions at the time
    • Single-lab studies
    • Structural basis of DJ-1/RREB1 cooperation unknown
  7. 2014 High

    Established evolutionary conservation of RREB1 DNA-binding and transcriptional-attenuation function through cross-species rescue of the Drosophila Hindsight ortholog.

    Evidence In vitro DNA binding, polytene chromosome mapping, and human RREB1 rescue of hnt germ band retraction phenotype

    PMID:24418439

    Open questions at the time
    • Conserved mammalian target genes not enumerated
    • Functional role of individual zinc fingers not dissected
  8. 2018 High

    Revealed a neuronal function: the RREB1 ortholog Pebbled is required for injury-induced axon death and acts within the dSarm/SARM1 axon-degeneration cascade, rescuable by human RREB1.

    Evidence Drosophila loss-of-function genetics, axotomy assays, genetic epistasis with dsarm, and human RREB1 rescue

    PMID:29295933

    Open questions at the time
    • Mammalian transcriptional targets in axon death not defined
    • Mechanistic link to SARM1 signaling unresolved
  9. 2020 High

    Defined the central EMT mechanism and a chromatin-modifying mode: RREB1 recruits SMAD factors to the SNAIL promoter to drive EMT, and recruits a Sin3a–KDM1A complex to MAPK gene promoters, with haploinsufficiency causing a Noonan-like RASopathy.

    Evidence Co-IP, ChIP-seq, biochemical reconstitution of RREB1-SMAD, CRISPR/KO, and Rreb1 hemizygous mouse modeling with H3K4 methylation analysis

    PMID:31915377 PMID:32938917

    Open questions at the time
    • Determinants directing RREB1 to activator vs repressor complexes not resolved
    • Full set of co-occupied SMAD/RREB1 genomic loci not exhaustively defined
  10. 2021 High

    Extended the developmental role in vivo: Rreb1 loss disrupts vasculogenesis, cytoskeletal/adherens-junction organization, and causes ectopic epithelial cell exit, linking embryonic and metastatic cell behaviors.

    Evidence Rreb1 knockout mouse embryos with RNA-seq, immunofluorescence (F-actin, E-cadherin), and histology

    PMID:33929320

    Open questions at the time
    • Direct cytoskeletal target genes not all validated by binding
    • Tissue-specific contributions not separated from systemic effects
  11. 2021 Medium

    Identified post-translational regulation of RREB1: miR-26a-driven deacetylation at Lys-60 enables AKT1 promoter binding and glycolytic signaling in colorectal cancer.

    Evidence Quantitative proteomics, Lys-60 mutagenesis, ChIP, reporter, and xenograft assays

    PMID:34419497

    Open questions at the time
    • Acetyltransferase/deacetylase enzymes acting on Lys-60 not identified
    • Single lab
  12. 2024 High

    Established RREB1 as essential for mammalian neuronal survival, regulating microtubule-cytoskeleton and endomembrane/autophagy genes whose loss causes Purkinje degeneration and proteostatic inclusions.

    Evidence Spontaneous Rreb1 mouse mutant with ChIP-seq, RNA-seq, dendritic morphology, and P62/ubiquitin immunofluorescence

    PMID:38198538

    Open questions at the time
    • Causal target gene driving autophagy defect not pinpointed
    • Relationship to RAS/MAPK regulation in neurons not directly tested
  13. 2024 Medium

    Connected RREB1 to SUMOylation biology and chemoresistance: it activates UBC9 to elevate global SUMOylation, and SUMOylated RREB1 binds KDM1A to drive thymidylate synthase/TK1 and Chk1-mediated DDR.

    Evidence ChIP, reporter, SUMOylation/deSUMOylation assays, Co-IP, and 5-FU resistance assays in colorectal cancer cells

    PMID:39108750 PMID:39991628

    Open questions at the time
    • SUMO acceptor sites on RREB1 not mapped
    • Single-lab findings without independent replication
  14. 2024 Medium

    Implicated RREB1 in additional tissue programs — adipocyte/osteoblast lineage balance and Sertoli cell maturation/spermatogenesis via Wt1 and Fshr regulation.

    Evidence Rreb1+/- mouse and human adipocyte differentiation assays (preprint); in vivo siRNA knockdown with Wt1 promoter reporter in mouse testis

    PMID:38248872 PMID:39131393

    Open questions at the time
    • Adipogenesis data are preprint, not peer-reviewed
    • Direct vs indirect target distinction incomplete in some programs
  15. 2024 Low

    Reported a candidate upstream link between m6A machinery and RREB1 through a METTL3-RREB1 physical interaction.

    Evidence Co-IP and domain mapping identifying the METTL3 N-terminus as the interacting region

    PMID:39278095

    Open questions at the time
    • Single Co-IP with no functional follow-up reported
    • Consequence for RREB1 mRNA or protein undefined
  16. 2026 Medium

    Defined a signaling-transcription-metabolism axis in glioma stem cells where a NIBAN2-FLII complex promotes RREB1 nuclear translocation and RREB1 activates NIBAN2/CD44/LDHA, plus an FMR1-VEGFA angiogenic program in colorectal cancer.

    Evidence Co-IP, nuclear fractionation, ChIP, RNA-seq/metabolomics in glioma models; ChIP-qPCR, reporter, and tube-formation/CAM assays for FMR1-VEGFA

    PMID:41736673 PMID:42214628

    Open questions at the time
    • Single-lab studies
    • Generalizability of these axes beyond the tested tumor contexts unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RREB1 is directed to activate versus repress a given promoter — the determinants selecting between SMAD/DJ-1 coactivators and CtBP/Sin3a-KDM1A corepressors, and how post-translational marks (acetylation, SUMOylation) and partner availability set this choice — remains unresolved.
  • No structural model of RREB1 in complex with coactivator or corepressor machinery
  • Genome-wide rules governing activator vs repressor target selection unknown
  • Cross-talk between neuronal RAS/MAPK regulation and oncogenic RAS effector roles 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 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 3 GO:0000228 nuclear chromosome 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1266738 Developmental Biology 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-112316 Neuronal System 2
Partners
CTBPDJ-1FLIIKDM1AMETTL3SFPQSIN3ASMAD
Complex memberships
CtBP co-repressor complexNIBAN2-FLII-RREB1 complexRREB1-SMAD complexRREB1-Sin3a-KDM1A complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 RREB-1 is a zinc finger transcription factor that binds to the Ras-responsive element (RRE) in the calcitonin gene promoter (consensus binding site CCCCAAACCACCCC) and, upon overexpression, mediates Ras- and Raf-induced transactivation of the calcitonin gene promoter in medullary thyroid cancer cells. Affinity screening/cDNA cloning, DNase I protection assay, reporter transactivation assay with overexpression Molecular and cellular biology High 8816445
2008 RREB1 (mammalian homolog of Drosophila Hindsight/HNT) is required for collective cell migration; siRNA knockdown of RREB1 in MCF10A mammary epithelial cells inhibited collective migration in scratch-wound assays, suppressed surface activity, retarded cell spreading, and caused formation of immobile, tightly adherent colonies, indicating RREB1 reduces cell-cell adhesion to enable dynamic epithelial cell movements. siRNA knockdown, scratch-wound healing assay, live-cell imaging, Drosophila genetic analysis (hnt mutants) Current biology : CB High 18394891
2009 RREB-1 represses HLA-G transcriptional activity by binding three Ras-response elements within the HLA-G promoter; in HLA-G-negative cells, RREB-1 interacts with subunits of the CtBP co-repressor complex implicated in chromatin remodeling. Promoter pull-down assay followed by mass spectrometry, reporter assay, Co-IP (RREB-1 with CtBP complex subunits) Journal of immunology Medium 19890057
2009 RREB-1 binds the p53 core promoter element and transactivates p53 expression; upon genotoxic stress, RREB-1 recruitment to the p53 promoter increases, and RREB-1 silencing reduces p53 mRNA and protein levels and suppresses downstream p53 target gene expression, controlling apoptosis in a p53-dependent manner. ChIP, luciferase reporter assay, siRNA knockdown, qRT-PCR, Western blot The Biochemical journal Medium 19558368
2010 RREB-1 binds to a specific RRE site in the hZIP1 promoter and represses hZIP1 zinc transporter transcription in prostate cancer cells; this binding was demonstrated by gel shift and ChIP, and site-directed mutagenesis of the binding site relieved repression. Luciferase reporter assay, site-directed mutagenesis, EMSA (gel shift), ChIP The Prostate High 19802870
2011 Overexpression of RREB-1 decreases hZIP1 abundance at the plasma membrane of PC-3 prostate cancer cells, while siRNA knockdown of RREB-1 significantly increases hZIP1 expression, establishing RREB-1 as a transcriptional repressor of hZIP1 in vivo. Overexpression, siRNA knockdown, immunohistochemistry/Western blot The Prostate Medium 21360563
2012 RREB1 is activated by the MAPK pathway downstream of oncogenic KRAS and negatively represses the miR-143/145 promoter through interaction with two RREs, constituting a regulatory feedback loop where miR-143/145 in turn targets KRAS and RREB1. Reporter assay, ChIP, qRT-PCR, overexpression/knockdown, MAPK pathway inhibition Oncogene Medium 22751122
2013 DJ-1 acts as a coactivator by physically interacting with RREB1; the DJ-1/RREB1 complex (but not a DJ-1/Sp1 complex) binds to the RRE in the cholecystokinin (CCK) gene promoter, stimulating CCK transcription. DJ-1 knockout mice show reduced serum CCK levels. Co-immunoprecipitation, promoter binding assay, luciferase reporter, qRT-PCR, ELISA in DJ-1-knockout mice PloS one Medium 24348900
2014 The Drosophila HNT C-terminal region (containing the last five zinc fingers) binds DNA elements similar to those of human RREB-1; human RREB-1 expressed in Drosophila binds the same polytene chromosome sites as HNT, attenuates expression of hnt and nvy target genes, and rescues the germ band retraction phenotype, demonstrating functional conservation of DNA binding and transcriptional attenuation. In vitro DNA binding assay, polytene chromosome binding, rescue genetics, loss-of-function and overexpression in Drosophila Differentiation; research in biological diversity High 24418439
2017 RREB1 cooperates with the lncRNA linc-ADAMTS5 to repress ADAMTS5 expression in nucleus pulposus cells; RREB1 is recruited to the ADAMTS5 promoter via a physical interaction with splicing factor SFPQ (facilitated by linc-ADAMTS5 binding to SFPQ), and this complex induces chromatin remodeling involving histone deacetylases to suppress ADAMTS5 transcription. RNA pulldown, RIP, in vitro binding assay, ChIP, gain/loss-of-function studies Clinical science Medium 28341660
2018 The Drosophila RREB1 ortholog Pebbled (Peb) is required in glutamatergic sensory neurons for axon death after injury; loss of peb results in preservation or incomplete fragmentation of severed axons, and human RREB1 rescues peb mutant phenotypes. Dominant genetic interactions between peb and dsarm place peb/RREB1 in the axon death signaling cascade. Drosophila genetics (loss-of-function mutants), human RREB1 rescue, axotomy assay, genetic epistasis with dsarm Proceedings of the National Academy of Sciences of the United States of America High 29295933
2020 RREB1 is a MAPK-activated RAS transcriptional effector that physically recruits TGF-β-activated SMAD transcription factors to the SNAIL promoter; RREB1 and SMAD together drive expression of SNAIL and context-dependent EMT gene programs. In carcinoma cells, RREB1-SMAD drive fibrogenic EMT; in mouse epiblast progenitors, RREB1-Nodal-SMAD drive developmental EMT/gastrulation. Co-IP, ChIP-seq, reporter assay, CRISPR/KO, mouse embryo genetics, biochemical reconstitution of RREB1-SMAD complex Nature High 31915377
2020 Rreb1 haploinsufficiency in mice sensitizes MAPK signaling; RREB1 recruits Sin3a and Kdm1a (KDM1A) to MAPK pathway gene promoters to control H3K4 methylation, thereby epigenetically reprogramming RAS-MAPK target gene expression. Loss of one Rreb1 allele phenocopies Noonan syndrome features (orbital hypertelorism, cardiac hypertrophy). Rreb1 hemizygous mouse model, ChIP, Co-immunoprecipitation (RREB1-Sin3a-Kdm1a complex), H3K4 methylation analysis, MAPK signaling assays Nature communications High 32938917
2021 Loss of Rreb1 in mouse embryos reduces expression of vasculogenic factors, causes cardiovascular defects and embryonic lethality; during gastrulation, absence of Rreb1 upregulates cytoskeleton-associated genes, alters F-actin and adherens junction organization in the epiblast, and causes ectopic exit of cells through the basement membrane, paralleling metastatic behavior. Rreb1 knockout mouse model, immunofluorescence (F-actin, E-cadherin), RNA-seq, histology eLife High 33929320
2021 miR-26a promotes deacetylation of RREB1 at the Lys-60 residue; deacetylated RREB1 binds the AKT1 promoter to activate AKT transcription and downstream glycolytic signaling in colorectal cancer cells. Quantitative proteomics, ChIP, luciferase reporter, loss-of-function analysis, site-specific mutagenesis of Lys-60, xenograft mouse model Cancer letters Medium 34419497
2022 Ras signaling and RREB1 are required for dissociation of medial edge epithelial (MEE) cells during murine palatogenesis; siRNA knockdown of Rreb1 in palatal organ culture inhibited MEE cell dissociation and caused palatal fusion defects, placing RREB1 downstream of RAS in this EMT-like process. siRNA knockdown in palatal organ culture, pan-Ras inhibitor treatment, morphological analysis Disease models & mechanisms Medium 34897389
2024 RREB1 is essential for neuronal survival in the mammalian brain; a spontaneous mouse mutation in the nervous-system-enriched Rreb1 transcript causes progressive Purkinje cell loss and ataxia. ChIP-seq and RNA-seq reveal RREB1 regulates genes associated with the microtubule cytoskeleton and the endomembrane system; loss of RREB1 disrupts dendritic complexity, reduces autophagosomes/lysosomes, and causes accumulation of P62- and ubiquitin-positive inclusions. Spontaneous mouse mutant, ChIP-seq, RNA-seq, immunofluorescence (P62, ubiquitin, autophagosomes), dendritic morphology analysis Science advances High 38198538
2024 RREB1 directly activates transcription of UBC9 by binding its promoter, thereby elevating global protein SUMOylation (SUMO2/3) in colorectal cancer cells, which contributes to 5-fluorouracil resistance. ChIP-qPCR, luciferase reporter assay, overexpression/knockdown, Western blot for SUMOylation Frontiers in pharmacology Medium 39108750
2024 SUMOylated RREB1 physically interacts with KDM1A; this RREB1-KDM1A complex elevates expression of thymidylate synthase (TS) and thymidine kinase (TK1) and enhances activation of Chk1-mediated DNA damage response. DeSUMOylation of RREB1 reduces the RREB1-KDM1A interaction, decreasing TS expression and attenuating DDR pathway activation. Co-immunoprecipitation, SUMOylation assay, ChIP, Western blot, KDM1A knockdown, 5-FU resistance assay MedComm Medium 39991628
2024 METTL3 physically interacts with RREB1 (an enriched METTL3 mRNA target), with the N-terminus of METTL3 as the primary interacting domain, revealing a novel regulatory connection between the m6A methylation machinery and RREB1. Co-immunoprecipitation, domain mapping Biochemical and biophysical research communications Low 39278095
2024 Loss of RREB1 in mouse and human adipocyte precursor cells decreases adipogenic gene expression and activates transcription of genes associated with osteoblast differentiation; global Rreb1+/- mice on high-fat diet show reduced fat mass and adipocyte size, with smaller, more insulin-sensitive subcutaneous adipocytes in certain conditions. Global heterozygous Rreb1+/- mouse model, adipogenic gene expression analysis (RNA-seq), adipocyte differentiation assays in mouse and human cells, in vivo body composition bioRxivpreprint Medium 39131393
2024 RREB1 is required for Sertoli cell maturation and spermatogenesis in mice; knockdown of Rreb1 causes defective blood-testis barrier structure, decreased expression of Sertoli cell maturity markers, and oligoasthenoteratozoospermia. Mechanistically, RREB1 directly activates the Wt1 promoter and positively regulates Fshr transcription; RREB1 knockdown destabilizes SMAD3 and reduces Wt1, Par6b, and E-cadherin expression. siRNA knockdown in mice (in vivo), promoter-reporter luciferase assay, Western blot, immunofluorescence, spermatogenesis phenotyping Zygote Medium 38248872
2025 Loss of Drosophila Peb (RREB1 ortholog) results in excessive RAS/MAPK pathway activation, causing adult-onset progressive motor axonal degeneration and NMJ degeneration; pharmacological inhibition of MEK1/2 with mirdametinib rescues peb mutant neurodegeneration, establishing that Peb/RREB1 normally functions as a transcriptional negative regulator of RAS/MAPK pathway target genes to maintain axonal integrity. Drosophila forward genetic screen, loss-of-function genetics, MAPK pathway activity assays, MEK inhibitor pharmacological rescue bioRxivpreprint Medium
2007 RREB-1 is a transcriptional effector downstream of the Ral GTPases (RalA and RalB) in bladder cancer cells; computational analysis of RRE motifs in promoters of Ral-regulated genes, verified experimentally, identified RREB-1 as a target of Ral signaling. siRNA depletion of RalA/RalB, microarray gene expression profiling, computational promoter analysis, experimental verification of RREB-1 as Ral target Oncogene Low 17496927
2013 RREB1 positively regulates ZIP3 zinc transporter expression in pancreatic cells; downregulation of RREB1 in Panc1 cells reduces ZIP3, which reduces zinc uptake and accumulation, relieving zinc cytotoxicity in developing malignant cells. RREB1 overexpression/siRNA knockdown, ZIP3 expression analysis, zinc accumulation assay, cell proliferation assay Cancer biology & therapy Medium 25050557
2023 RREB1 transcriptionally activates the SNHG4 lncRNA promoter; SNHG4 in turn acts as a ceRNA sponging let-7a miRNA, which itself targets RREB1, establishing a let-7a/RREB1/SNHG4 positive feedback loop that promotes prostate cancer cell survival and enzalutamide resistance. ChIP assay, luciferase reporter assay, RNA immunoprecipitation, qRT-PCR, in vitro/in vivo functional assays Journal of experimental & clinical cancer research Medium 37596700
2026 RREB1 transcriptionally activates FMR1 by directly binding the FMR1 promoter; FMR1 in turn enhances VEGFA expression and secretion, activating MAPK and PI3K signaling in endothelial cells to promote angiogenesis in colorectal cancer. ChIP-qPCR, luciferase reporter assay, HUVEC tube formation, CAM assay, siRNA knockdown, co-expression analysis in CRC tissues Biochimica et biophysica acta. Molecular cell research Medium 42214628
2021 RREB1 knockdown in gastric cancer cells enhances p16 expression and inhibits cell proliferation in vitro and in vivo, identifying RREB1 as a negative regulator of p16 in gastric cancer. Lentiviral RREB1 knockdown/overexpression, MTT, colony formation, cell cycle assay, xenograft mouse model, Western blot for p16 Cell cycle Low 34666611
2026 In glioma stem cells, NIBAN2 directly binds FLII and enhances the FLII-RREB1 interaction, promoting RREB1 nuclear translocation; the NIBAN2-FLII-RREB1 complex activates TLR3 signaling. RREB1 also transcriptionally upregulates NIBAN2 and CD44 and promotes LDHA expression, establishing a feed-forward signaling-transcription-metabolism axis. Co-immunoprecipitation, nuclear fractionation, ChIP, RNA-seq, metabolomics, in vitro and in vivo tumor models Advanced science Medium 41736673

Source papers

Stage 0 corpus · 64 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 TGF-β orchestrates fibrogenic and developmental EMTs via the RAS effector RREB1. Nature 415 31915377
1996 RREB-1, a novel zinc finger protein, is involved in the differentiation response to Ras in human medullary thyroid carcinomas. Molecular and cellular biology 133 8816445
2012 RREB1 repressed miR-143/145 modulates KRAS signaling through downregulation of multiple targets. Oncogene 123 22751122
2019 RREB1-induced upregulation of the lncRNA AGAP2-AS1 regulates the proliferation and migration of pancreatic cancer partly through suppressing ANKRD1 and ANGPTL4. Cell death & disease 95 30814490
2010 Sensitivity of fluorescence in situ hybridization for melanoma diagnosis using RREB1, MYB, Cep6, and 11q13 probes in melanoma subtypes. Archives of dermatology 87 20231497
2008 Regulation of cell adhesion and collective cell migration by hindsight and its human homolog RREB1. Current biology : CB 72 18394891
2018 Ectomesenchymal Chondromyxoid Tumor: A Neoplasm Characterized by Recurrent RREB1-MKL2 Fusions. The American journal of surgical pathology 60 29912715
2009 RREB-1 is a transcriptional repressor of HLA-G. Journal of immunology (Baltimore, Md. : 1950) 57 19890057
2020 Transcription Factor RREB1: from Target Genes towards Biological Functions. International journal of biological sciences 49 32210733
2011 hZIP1 zinc transporter down-regulation in prostate cancer involves the overexpression of ras responsive element binding protein-1 (RREB-1). The Prostate 48 21360563
2010 Ras responsive element binding protein-1 (RREB-1) down-regulates hZIP1 expression in prostate cancer cells. The Prostate 39 19802870
2018 Transcription factor Pebbled/RREB1 regulates injury-induced axon degeneration. Proceedings of the National Academy of Sciences of the United States of America 38 29295933
2014 The cytotoxic role of RREB1, ZIP3 zinc transporter, and zinc in human pancreatic adenocarcinoma. Cancer biology & therapy 37 25050557
2009 DNA damage signalling recruits RREB-1 to the p53 tumour suppressor promoter. The Biochemical journal 37 19558368
2023 LncRNA SNHG4 promotes prostate cancer cell survival and resistance to enzalutamide through a let-7a/RREB1 positive feedback loop and a ceRNA network. Journal of experimental & clinical cancer research : CR 36 37596700
2017 The noncoding RNA linc-ADAMTS5 cooperates with RREB1 to protect from intervertebral disc degeneration through inhibiting ADAMTS5 expression. Clinical science (London, England : 1979) 36 28341660
2020 Haploinsufficiency of RREB1 causes a Noonan-like RASopathy via epigenetic reprogramming of RAS-MAPK pathway genes. Nature communications 31 32938917
2012 Evidence for changes in RREB-1, ZIP3, and Zinc in the early development of pancreatic adenocarcinoma. Journal of gastrointestinal cancer 31 22427155
2023 The U2AF65/circNCAPG/RREB1 feedback loop promotes malignant phenotypes of glioma stem cells through activating the TGF-β pathway. Cell death & disease 28 36635261
2021 miR-26a enhances colorectal cancer cell growth by targeting RREB1 deacetylation to activate AKT-mediated glycolysis. Cancer letters 27 34419497
2018 RREB1-MKL2 fusion in biphenotypic "oropharyngeal" sarcoma: New entity or part of the spectrum of biphenotypic sinonasal sarcomas? Genes, chromosomes & cancer 27 29266774
2014 The ras responsive transcription factor RREB1 is a novel candidate gene for type 2 diabetes associated end-stage kidney disease. Human molecular genetics 27 25027322
2011 RREB1 transcription factor splice variants in urologic cancer. The American journal of pathology 20 21703425
2007 Expression profiling of Ral-depleted bladder cancer cells identifies RREB-1 as a novel transcriptional Ral effector. Oncogene 20 17496927
2022 RREB1::MRTFB fusion-positive extra-glossal mesenchymal neoplasms: A series of five cases expanding their anatomic distribution and highlighting significant morphological and phenotypic diversity. Genes, chromosomes & cancer 19 35763541
2013 Transcriptional activation of the cholecystokinin gene by DJ-1 through interaction of DJ-1 with RREB1 and the effect of DJ-1 on the cholecystokinin level in mice. PloS one 19 24348900
2018 Sleeping Beauty Screen Identifies RREB1 and Other Genetic Drivers in Human B-cell Lymphoma. Molecular cancer research : MCR 18 30355676
2020 Mesenchymal tumours with RREB1-MRTFB fusion involving the mediastinum: extra-glossal ectomesenchymal chondromyxoid tumours? Histopathology 16 31991003
2023 Crocin Suppresses Colorectal Cancer Cell Proliferation by Regulating miR-143/145 and KRAS/RREB1 Pathways. Anti-cancer agents in medicinal chemistry 13 37464834
2021 RREB1-MKL2 fusion in a spindle cell sinonasal sarcoma: biphenotypic sinonasal sarcoma or ectomesenchymal chondromyxoid tumor in an unusual site? Genes, chromosomes & cancer 13 33715240
2021 The transcription factor Rreb1 regulates epithelial architecture, invasiveness, and vasculogenesis in early mouse embryos. eLife 12 33929320
2013 Complex three-way translocation involving MLL, ELL, RREB1, and CMAHP genes in an infant with acute myeloid leukemia and t(6;19;11)(p22.2;p13.1;q23.3). Cytogenetic and genome research 12 23735562
2020 Functional Analysis of Two Zinc (Zn) Transporters (ZIP3 and ZIP8) Promoters and Their Distinct Response to MTF1 and RREB1 in the Regulation of Zn Metabolism. International journal of molecular sciences 11 32858813
2014 Drosophila Hindsight and mammalian RREB-1 are evolutionarily conserved DNA-binding transcriptional attenuators. Differentiation; research in biological diversity 11 24418439
1997 Analysis of the structure and expression of the chicken gene encoding a homolog of the human RREB-1 transcription factor. Gene 11 9427563
2024 RREB1 regulates neuronal proteostasis and the microtubule network. Science advances 10 38198538
2020 RREB1 Integrates TGF-β and RAS Signals to Drive EMT. Developmental cell 9 32049037
2012 Proteomic identification of RREB1, PDE6B, and CD209 up-regulated in primitive gut tube differentiated from human embryonic stem cells. Pancreas 9 21792086
2024 RREB1-mediated SUMOylation enhancement promotes chemoresistance partially by transcriptionally upregulating UBC9 in colorectal cancer. Frontiers in pharmacology 8 39108750
2025 The SUMOylated RREB1 interacts with KDM1A to induce 5-fluorouracil resistance via upregulating thymidylate synthase and activating DNA damage response pathway in colorectal cancer. MedComm 6 39991628
2022 A novel method to assess copy number variation in melanoma: Droplet digital PCR for precise quantitation of the RREB1 gene in formalin-fixed, paraffin-embedded melanocytic neoplasms, a proof-of-concept study. Journal of cutaneous pathology 6 36325821
2016 Performance Testing of RREB1, MYB, and CCND1 Fluorescence In Situ Hybridization in Spindle-Cell and Desmoplastic Melanoma Argues for a Two-Step Test Algorithm. International journal of surgical pathology 6 27899693
2022 Ras signaling and RREB1 are required for the dissociation of medial edge epithelial cells in murine palatogenesis. Disease models & mechanisms 5 34897389
2021 Regulatory SNP of RREB1 is Associated With Bone Mineral Density in Chinese Postmenopausal Osteoporosis Patients. Frontiers in genetics 4 34868232
2024 A Proteomics Approach Identifies RREB1 as a Crucial Molecular Target of Imidazo-Pyrazole Treatment in SKMEL-28 Melanoma Cells. International journal of molecular sciences 3 38928466
2022 circXRCC5 foster gastric cancer growth and metastasis by the HNRNPC/circXRCC5/miR-655-3p/RREB1/UBA2 positive feedback loop. Cancer gene therapy 3 35661832
2025 An extralingual Ectomesenchymal chondromyxoid tumor with RREB1::MRTFB fusion: a rare case report of plantar fascia involvement. Diagnostic pathology 2 40022218
2024 The first case of a point pathogenic variant in the RREB1 gene in Noonan-like Rasopathy. Clinical genetics 2 38332451
2022 A Novel Tongue-Based Tumor With an RREB1-MRTFB Fusion: Variant Rhabdomyosarcoma or Aggressive Variant of Ectomesenchymal Chondromyxoid Tumor. Cureus 2 36726902
2021 Knockdown of RREB1 inhibits cell proliferation via enhanced p16 expression in gastric cancer. Cell cycle (Georgetown, Tex.) 2 34666611
2025 Truncating Variants in RREB1 Cause a Novel RASopathy Syndrome of Congenital Heart Disease, Genitourinary Malformations, and Developmental Delay. American journal of medical genetics. Part A 1 40418122
2025 An epithelioid hemangioendothelioma with a novel RREB1::TFE3 gene fusion. Virchows Archiv : an international journal of pathology 1 40650764
2024 Rreb1 is a key transcription factor in Sertoli cell maturation and function and spermatogenesis in mouse. Zygote (Cambridge, England) 1 38248872
2024 Loss of RREB1 reduces adipogenesis and improves insulin sensitivity in mouse and human adipocytes. bioRxiv : the preprint server for biology 1 39131393
2022 RREB1 promotes the development of parafollicular carcinogenesis through the Ras-Raf-1-ELK3 signaling pathway. Nucleosides, nucleotides & nucleic acids 1 35737446
2026 NIBAN2/FLII/RREB1 Axis Drives Glioma Stem Cell Malignancy via TLR3 Pathway Activation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41736673
2026 SIRT6 alleviates ischemic injury via orchestrating the RREB1/Snail and STC1/Smad7 signaling pathways to regulate endothelial-mesenchymal transition. Science China. Life sciences 0 41882317
2026 RBM15 transcription activated by EGR1 stimulates gastric cancer proliferation and metastasis by enhancing m6A modification of RREB1. Functional & integrative genomics 0 42213215
2026 RREB1-driven FMR1 upregulation promotes colorectal cancer angiogenesis via VEGFA-mediated MAPK/PI3K signaling activation. Biochimica et biophysica acta. Molecular cell research 0 42214628
2025 First Report of a Novel Pathogenic Variant in the RREB1 Gene Associated With Obesity and Metabolic Syndrome. Clinical genetics 0 40518752
2025 Unusual Locations of Extra-Glossal Ectomesenchymal Chondromyxoid Tumors with RREB1-MRTFB Gene Fusions: A Report of Two Cases. Head and neck pathology 0 40658185
2025 Cutaneous/subcutaneous RREB1::MRTFB fusion-positive extra-glossal mesenchymal neoplasm-two cases expanding the anatomical spectrum of an emerging entity. Virchows Archiv : an international journal of pathology 0 41449216
2024 A novel interaction between RNA m6A methyltransferase METTL3 and RREB1. Biochemical and biophysical research communications 0 39278095
2024 Suppression of KLF5 targets RREB1 to restrain the proliferation of ovarian cancer cells through ERK/MAPK signaling pathway. 3 Biotech 0 39676889

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