Affinage

RREB1

Ras-responsive element-binding protein 1 · UniProt Q92766

Length
1687 aa
Mass
181.4 kDa
Annotated
2026-04-28
100 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RREB1 is a multi-zinc-finger transcription factor that functions as a RAS–MAPK effector, integrating mitogenic and morphogenetic signaling into chromatin-level transcriptional programs that control epithelial-to-mesenchymal transition (EMT), cell migration, neuronal survival, and proteostasis. RREB1 binds RAS-responsive elements in target promoters and, upon MAPK-dependent activation, recruits TGF-β-activated SMAD complexes to drive SNAIL expression and fibrogenic/mesendoderm gene programs during both carcinoma EMT and gastrulation (PMID:31915377), while also partnering with the Sin3A–KDM1A corepressor complex to modulate H3K4 methylation at MAPK pathway genes and restrain RAS signaling output (PMID:32938917, PMID:39991628). Through additional interactions with the CtBP chromatin-remodeling complex and HDAC-containing assemblies, RREB1 epigenetically represses diverse targets including HLA-G, miR-143/145, hZIP1, and ADAMTS5 (PMID:19890057, PMID:22751122, PMID:19802870, PMID:28341660). A nervous-system-enriched Rreb1 transcript is essential for Purkinje cell survival, with its loss causing impaired autophagy–lysosome proteostasis, cytoskeletal disorganization, and progressive cerebellar degeneration (PMID:38198538).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1996 High

    Establishing that RREB1 is a zinc-finger transcription factor that directly mediates RAS/RAF-induced gene activation by binding a defined RAS-responsive element (RRE) in the calcitonin promoter answered the question of how RAS signaling converges on specific promoter sequences.

    Evidence cDNA cloning, DNase I footprinting, and reporter transactivation in medullary thyroid carcinoma cells with RAS/RAF overexpression

    PMID:8816445

    Open questions at the time
    • Identity of the kinase that directly phosphorylates/activates RREB1 was not determined
    • Full spectrum of RRE-containing target genes unknown
    • Structural basis of zinc-finger–RRE recognition not resolved
  2. 2007 Medium

    Placing RREB1 downstream of Ral GTPases in addition to RAF broadened its role as a convergence node for multiple RAS-family effector pathways.

    Evidence siRNA depletion of RalA/RalB coupled with microarray profiling and upstream motif analysis in bladder cancer cells

    PMID:17496927

    Open questions at the time
    • Direct physical interaction between Ral pathway components and RREB1 was not shown
    • Whether Ral activates RREB1 independently of MAPK unclear
  3. 2008 High

    Demonstrating that RREB1 (and its Drosophila ortholog HNT) is required for collective cell migration and cell–cell adhesion remodeling via JNK and STAT pathways revealed a conserved morphogenetic function beyond simple transcriptional activation.

    Evidence Drosophila loss-of-function mutants in follicle cells and siRNA knockdown with scratch-wound assays in mammalian MCF10A cells

    PMID:18394891

    Open questions at the time
    • Direct transcriptional targets mediating the migration phenotype not identified
    • Whether JNK/STAT regulation is direct or indirect unknown
  4. 2009 Medium

    Identifying RREB1 as a repressor that recruits the CtBP chromatin-remodeling complex to silence HLA-G, and as a direct transactivator of p53 under genotoxic stress, established its dual activator/repressor capacity depending on cofactor context.

    Evidence Promoter pull-down with MS, Co-IP of RREB1–CtBP subunits (HLA-G); ChIP and siRNA with apoptosis readouts (p53)

    PMID:19558368 PMID:19890057

    Open questions at the time
    • Determinants that switch RREB1 between activation and repression not defined
    • CtBP complex interaction validated in single lab only
  5. 2010 High

    Showing that RREB1 directly represses the zinc transporter hZIP1 via promoter binding connected RREB1 to zinc homeostasis, a pathway later extended to ZIP3 in pancreatic cells.

    Evidence EMSA, ChIP, promoter mutagenesis, and gain/loss-of-function in prostate cancer cells; confirmed in tissue microarrays and extended to ZIP3 in pancreatic cells

    PMID:19802870 PMID:21360563 PMID:25050557

    Open questions at the time
    • How RREB1 switches from repression (hZIP1) to activation (ZIP3) at different zinc transporter promoters unresolved
    • In vivo relevance in zinc-dependent tumor biology not fully tested
  6. 2012 High

    Elucidating that MAPK-activated RREB1 represses the miR-143/145 cluster, which in turn targets KRAS and RREB1, revealed a self-reinforcing KRAS–RREB1–miRNA feedback loop in colorectal cancer.

    Evidence ChIP, luciferase reporters, miRNA overexpression, MAPK inhibitor treatment in colorectal cancer cells

    PMID:22751122

    Open questions at the time
    • Whether this feedback loop operates in normal colonic epithelium unknown
    • Quantitative parameters of the feedback circuit (thresholds, dynamics) not modeled
  7. 2014 High

    Cross-species rescue experiments showing human RREB1 substitutes for Drosophila HNT at identical chromosomal binding sites proved deep functional conservation of the DNA-binding and transcriptional domains.

    Evidence Polytene chromosome mapping, in vitro DNA binding, cross-species rescue of germ-band retraction in Drosophila

    PMID:24418439

    Open questions at the time
    • Whether cofactor recruitment is also conserved across species not tested
    • Mammalian genomic binding-site repertoire not yet mapped
  8. 2017 Medium

    Demonstrating that RREB1 recruits a lncRNA (linc-ADAMTS5) and SFPQ to the ADAMTS5 promoter for HDAC-mediated repression expanded its mechanism to include noncoding RNA-guided chromatin remodeling.

    Evidence RNA pull-down, RIP, ChIP, and gain/loss-of-function in nucleus pulposus cells

    PMID:28341660

    Open questions at the time
    • Generality of RREB1–lncRNA partnerships at other loci not explored
    • Specific HDAC isoform recruited not identified
  9. 2018 High

    Genetic epistasis placing RREB1/Pebbled upstream of dSarm in Wallerian degeneration—with cross-species rescue—established RREB1 as a transcriptional regulator of the axon death signaling pathway.

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

    PMID:29295933

    Open questions at the time
    • Direct transcriptional targets through which RREB1 promotes axon degeneration not identified
    • Whether RREB1 acts in mammalian Wallerian degeneration in vivo unknown
  10. 2020 High

    ChIP-seq and knockout studies showing that MAPK-activated RREB1 physically recruits TGF-β-activated SMADs to the SNAIL promoter and EMT loci in carcinoma and embryonic contexts answered the long-standing question of how RAS and TGF-β pathways converge at chromatin to drive EMT.

    Evidence ChIP-seq, ATAC-seq, Co-IP of RREB1–SMADs, RREB1 KO/KD, mouse epiblast progenitors, carcinoma EMT models

    PMID:31915377

    Open questions at the time
    • Structural basis of RREB1–SMAD interaction not resolved
    • Whether RREB1 recruits SMADs at non-EMT loci is unexplored
  11. 2020 High

    Demonstrating that RREB1 recruits the Sin3A–KDM1A corepressor to control H3K4 methylation at MAPK pathway genes, and that Rreb1 haploinsufficiency causes Noonan-like features in mice, established RREB1 as an epigenetic rheostat of RAS–MAPK signaling strength.

    Evidence Co-IP of RREB1 with Sin3A and KDM1A, ChIP for H3K4me marks, Rreb1 hemizygous mouse model with cardiac and craniofacial phenotyping

    PMID:32938917

    Open questions at the time
    • Whether human RREB1 haploinsufficiency causes RASopathy-spectrum disease not established
    • Full set of MAPK pathway promoters regulated via this mechanism not defined
  12. 2021 High

    Rreb1-null mouse embryos revealed that RREB1 normally restrains cytoskeletal gene expression to maintain epiblast epithelial integrity, with its loss causing F-actin and adherens junction disorganization and embryonic lethality.

    Evidence Rreb1 knockout mouse, RNA-seq, immunofluorescence of F-actin/adherens junctions

    PMID:33929320

    Open questions at the time
    • Whether cytoskeletal gene derepression is a direct or indirect consequence of RREB1 loss not distinguished
    • Relationship between this epithelial integrity role and the EMT-promoting SMAD-recruitment role is paradoxical and unresolved
  13. 2024 High

    Identification of a nervous-system-enriched Rreb1 transcript essential for Purkinje cell survival—with its loss causing defective autophagy–lysosome proteostasis, dendritic simplification, and progressive cerebellar degeneration—expanded RREB1 function to neuronal maintenance and protein quality control.

    Evidence Spontaneous mouse mutation, ChIP-seq, RNA-seq, immunofluorescence for p62/ubiquitin inclusions and autophagosomes in Purkinje cells

    PMID:38198538

    Open questions at the time
    • Which specific RREB1 target genes mediate autophagy–lysosome regulation not determined
    • Whether human cerebellar ataxias harbor RREB1 mutations unknown
  14. 2024 Medium

    Showing that SUMOylation of RREB1 is required for its interaction with KDM1A and that RREB1 transcriptionally upregulates UBC9 (the SUMO E2 enzyme) revealed a SUMOylation-dependent self-amplifying loop controlling chemoresistance.

    Evidence Co-IP of RREB1–KDM1A, ChIP at TS/TK1 and UBC9 promoters, SUMOylation inhibitor rescue of 5-FU sensitivity in colorectal cancer cells

    PMID:39108750 PMID:39991628

    Open questions at the time
    • SUMOylation site(s) on RREB1 not mapped in this context
    • Whether the RREB1–UBC9 loop operates outside colorectal cancer not tested
    • Single-lab findings awaiting independent confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of RREB1 zinc-finger–DNA recognition and RREB1–SMAD interaction; the post-translational modification code (phosphorylation, acetylation, SUMOylation) that dictates cofactor choice; how RREB1 switches between activator and repressor modes at different loci; and whether human RREB1 loss-of-function mutations underlie neurodegenerative or RASopathy-spectrum diseases.
  • No crystal or cryo-EM structure of RREB1 or its complexes
  • Genome-wide binding-site atlas in human tissues incomplete
  • Physiological significance of acetylation at Lys-60 in non-cancer contexts unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 10 GO:0003677 DNA binding 6 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 7
Pathway
R-HSA-74160 Gene expression (Transcription) 9 R-HSA-4839726 Chromatin organization 4 R-HSA-1266738 Developmental Biology 3 R-HSA-112316 Neuronal System 2 R-HSA-9612973 Autophagy 1
Partners
CTBP1DJ-1EZH2KDM1ASFPQSIN3ASMAD2SMAD3
Complex memberships
CtBP chromatin-remodeling complexRREB1–SMAD complexSin3A/KDM1A corepressor complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 RREB1 (RREB-1) was cloned as a zinc finger transcription factor that binds to the Ras-responsive element (RRE) in the human calcitonin gene promoter (consensus: CCCCAAACCACCCC) and mediates RAS/RAF-induced transcriptional activation of the calcitonin gene in medullary thyroid carcinoma cells. Affinity screening/cDNA cloning, DNase I footprinting, reporter transactivation assays with RAS/RAF overexpression Molecular and cellular biology High 8816445
2008 HNT (Drosophila ortholog of RREB1) regulates collective cell migration and cell-cell adhesion by modulating JNK and STAT pathways in follicle cells; siRNA knockdown of mammalian RREB1 in MCF10A cells inhibited collective migration in scratch-wound assays, suppressed surface activity, retarded cell spreading, and led to immobile, tightly adherent colonies. Drosophila genetics (loss-of-function mutants), siRNA knockdown, scratch-wound healing assay, live imaging Current biology : CB High 18394891
2009 RREB-1 represses HLA-G transcription by binding three RREs in the HLA-G promoter; in HLA-G-negative cells, RREB-1 interacts with subunits of the CtBP chromatin-remodeling complex to mediate epigenetic repression. Promoter pull-down assay followed by mass spectrometry, luciferase reporter assays, Co-IP of 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 recruits to the p53 promoter and controls apoptosis in a p53-dependent manner. ChIP, siRNA knockdown, luciferase reporter assay, apoptosis assays The Biochemical journal Medium 19558368
2010 RREB-1 binds to the hZIP1 promoter and represses hZIP1 zinc transporter transcription in prostate cancer cells; RREB-1 overexpression decreases hZIP1 membrane abundance whereas siRNA knockdown increases it. Luciferase reporter assay, site-directed mutagenesis, gel shift (EMSA), ChIP, siRNA knockdown, RREB-1 overexpression The Prostate High 19802870
2011 RREB-1 overexpression in prostate cancer cells down-regulates hZIP1 zinc transporter, contributing to decreased zinc levels; inverse relationship between RREB-1 and hZIP1 confirmed in tissue microarrays. RREB-1 overexpression and siRNA knockdown in PC-3 cells, immunohistochemistry on tissue microarrays The Prostate Medium 21360563
2012 RREB1, activated by the MAPK pathway downstream of oncogenic KRAS, negatively regulates the miR-143/145 cluster by binding two RREs in the miR-143/145 promoter in colorectal cancer; miR-143/145 in turn target KRAS and RREB1, forming a feedback loop. ChIP, luciferase reporter assay, miRNA overexpression, siRNA knockdown, MAPK pathway inhibition Oncogene High 22751122
2013 DJ-1 physically interacts with RREB1 and the DJ-1/RREB1 complex binds the RRE in the cholecystokinin (CCK) gene promoter to activate CCK transcription; DJ-1-knockout mice show reduced serum CCK levels. Co-IP, ChIP, luciferase reporter assay, siRNA knockdown, DJ-1 knockout mice PloS one Medium 24348900
2014 Drosophila HNT (RREB1 ortholog) and human RREB1 bind to the same DNA elements (similar to known RREB-1 sites) via the C-terminal zinc fingers; RREB-1 expressed in Drosophila rescues hnt germ-band retraction phenotypes, attenuates hnt and nervy target gene transcription, and binds identical polytene chromosome sites as HNT, demonstrating functional conservation. Drosophila genetics (loss-of-function and overexpression), in vitro DNA binding, polytene chromosome mapping, cross-species rescue experiments Differentiation; research in biological diversity High 24418439
2014 RREB1 is a positive regulator of ZIP3 zinc transporter expression in pancreatic cells; RREB1 and ZIP3 downregulation is an early event in pancreatic adenocarcinoma development, and zinc accumulation via ZIP3 inhibits proliferation of Panc1 cells. siRNA knockdown, zinc uptake assays, cell proliferation assays, immunohistochemistry on tissue sections Cancer biology & therapy Medium 25050557
2018 Drosophila Pebbled (RREB1 ortholog) is required in glutamatergic sensory neurons to enable normal Wallerian axon degeneration; loss of peb results in axon preservation or partial fragmentation after axotomy, and peb/RREB1 genetically interacts with dsarm, placing it in the axon death signaling cascade; human RREB1 rescues peb mutant phenotypes. Drosophila genetics (loss-of-function), axotomy assays, genetic epistasis with dsarm, cross-species rescue with human RREB1 Proceedings of the National Academy of Sciences of the United States of America High 29295933
2018 RREB1-MKL2 (RREB1-MRTFB) fusion gene is identified in ~90% of ectomesenchymal chondromyxoid tumors; the RREB1 (exon 8)–MKL2 (exon 11) fusion product drives increased MKL2 expression, which regulates neural and myogenic differentiation. RNA sequencing, RT-PCR, FISH, Sanger sequencing The American journal of surgical pathology Medium 29912715
2020 RREB1 acts as a key partner of TGF-β-activated SMAD transcription factors in EMT: MAPK-activated RREB1 recruits TGF-β-activated SMADs to the SNAIL promoter, directly driving SNAIL expression and fibrogenic gene programs. In carcinoma cells, TGF-β–SMAD–RREB1 also drives intratumoral fibrosis and myofibroblast stimulation. In mouse epiblast, Nodal-SMAD and RREB1 combinatorially activate SNAIL and mesendoderm genes for gastrulation. Context-dependent chromatin accessibility determines the additional EMT gene targets activated. ChIP-seq, ATAC-seq, Co-IP of RREB1 with SMADs, reporter assays, RREB1 knockout/knockdown, mouse epiblast progenitor experiments, carcinoma cell EMT assays Nature High 31915377
2020 Rreb1 haploinsufficiency leads to sensitization of MAPK signaling; Rreb1 recruits the Sin3a corepressor and Kdm1a histone demethylase to control H3K4 methylation at MAPK pathway gene promoters, thereby acting as an epigenetic regulator of RAS-MAPK signaling. Rreb1 hemizygous mice display orbital hypertelorism and cardiac hypertrophy (Noonan-like phenotype). ChIP, Co-IP of RREB1 with Sin3a/Kdm1a, mouse knockout model, MAPK signaling assays, H3K4 methylation profiling Nature communications High 32938917
2021 Loss of Rreb1 in mouse embryos causes upregulation of cytoskeleton-associated genes, disorganization of F-actin and adherens junctions in the epiblast epithelium, ectopic exit of epiblast cells through the basement membrane, reduction of vasculogenic factor expression, cardiovascular defects, and embryonic lethality. Rreb1 knockout mouse model, RNA-seq, immunofluorescence of F-actin/adherens junctions, histology eLife High 33929320
2021 miR-26a improves deacetylation of RREB1 at Lys-60, which enables RREB1 to bind the AKT1 promoter and activate AKT transcription and downstream glycolytic signaling in colorectal cancer cells. Quantitative proteomics, ChIP, luciferase reporter assay, loss-of-function analysis, xenograft mouse model Cancer letters Medium 34419497
2022 RREB1 is required for RAS-mediated dissociation of medial edge epithelium (MEE) during murine palatal fusion; Rreb1 knockdown in palatal organ culture prevents MEE cell dissociation and causes palatal fusion defects, paralleling the role of RREB1 in EMT. Palatal organ culture, Rreb1 siRNA knockdown, pan-Ras inhibitor treatment, histological analysis Disease models & mechanisms Medium 34897389
2017 RREB1 binds to the ADAMTS5 promoter and recruits the noncoding RNA linc-ADAMTS5 together with SFPQ to induce chromatin remodeling via histone deacetylases (HDACs), resulting in repression of ADAMTS5 expression in nucleus pulposus cells. RNA pull-down, RIP, ChIP, in vitro binding assays, gain- and loss-of-function studies Clinical science Medium 28341660
2024 A nervous system-enriched Rreb1 transcript is essential for Purkinje cell survival in mice; loss of this transcript causes progressive cerebellar degeneration and ataxia. RREB1 targets include microtubule cytoskeleton genes and endomembrane system genes. Rreb1-deficient Purkinje cells exhibit reduced dendritic complexity, fewer autophagosomes and lysosomes, and accumulation of p62- and ubiquitin-positive inclusions, indicating impaired proteostasis. Spontaneous mouse mutation model, ChIP-seq, RNA-seq, immunofluorescence, histological analysis of Purkinje cells Science advances High 38198538
2024 RREB1 interacts with KDM1A (LSD1) histone demethylase; the RREB1–KDM1A complex elevates thymidylate synthase (TS) and thymidine kinase (TK1) expression and enhances Chk1-mediated DNA damage response, conferring 5-FU resistance in colorectal cancer. SUMOylation of RREB1 is required for its interaction with KDM1A; deSUMOylation reduces this interaction and re-sensitizes cells to 5-FU. Co-IP of RREB1 with KDM1A, ChIP, siRNA knockdown of KDM1A, SUMOylation inhibitor (ML-792), cell proliferation and apoptosis assays MedComm Medium 39991628
2024 RREB1 directly binds the UBC9 promoter to transcriptionally upregulate UBC9 (the sole E2 SUMO-conjugating enzyme), thereby enhancing global protein SUMOylation and conferring 5-FU resistance in colorectal cancer. ChIP, luciferase reporter assay, RREB1 overexpression and knockdown, SUMOylation inhibitor co-treatment Frontiers in pharmacology Medium 39108750
2007 RREB-1 is identified as a transcriptional effector downstream of Ral GTPases (RalA and RalB) in bladder cancer cells; Ral depletion modulates a transcriptional program that includes RREB-1 target genes, linking Ral signaling to RREB-1-mediated transcription. siRNA depletion of RalA/RalB, microarray gene expression profiling, computational upstream sequence analysis, experimental verification of RREB-1 as Ral target Oncogene Medium 17496927
2019 RREB1 activates transcription of the lncRNA AGAP2-AS1 in pancreatic cancer cells; AGAP2-AS1 in turn epigenetically suppresses ANKRD1 and ANGPTL4 by recruiting EZH2, promoting cell proliferation and migration. ChIP for RREB1 at AGAP2-AS1 promoter, RIP, EZH2 recruitment assay, gain/loss-of-function proliferation and invasion assays, xenograft model Cell death & disease Medium 30814490
2023 In glioma stem cells, circNCAPG stabilizes RREB1 protein and promotes its nuclear translocation to activate TGF-β1 signaling; RREB1 in turn transcriptionally upregulates U2AF65, which stabilizes circNCAPG, forming a positive feedback loop. RNA pull-down, RIP, ChIP, immunofluorescence for RREB1 nuclear translocation, gain/loss-of-function assays Cell death & disease Medium 36635261

Source papers

Stage 0 corpus · 100 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 403 31915377
2002 Clonal human (hNT) neuron grafts for stroke therapy: neuropathology in a patient 27 months after implantation. The American journal of pathology 185 11943704
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 121 22751122
1999 Functional synapses are formed between human NTera2 (NT2N, hNT) neurons grown on astrocytes. The Journal of comparative neurology 116 10213184
1999 Neural transplantation of human neuroteratocarcinoma (hNT) neurons into ischemic rats. A quantitative dose-response analysis of cell survival and behavioral recovery. Neuroscience 116 10366009
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
2002 Positive effect of transplantation of hNT neurons (NTera 2/D1 cell-line) in a model of familial amyotrophic lateral sclerosis. Experimental neurology 79 11922659
2008 Regulation of cell adhesion and collective cell migration by hindsight and its human homolog RREB1. Current biology : CB 71 18394891
1998 Viability and survival of hNT neurons determine degree of functional recovery in grafted ischemic rats. Neuroreport 60 9760130
2018 Ectomesenchymal Chondromyxoid Tumor: A Neoplasm Characterized by Recurrent RREB1-MKL2 Fusions. The American journal of surgical pathology 59 29912715
1999 Neural transplantation of hNT neurons for Huntington's disease. Cell transplantation 58 10338282
2009 RREB-1 is a transcriptional repressor of HLA-G. Journal of immunology (Baltimore, Md. : 1950) 57 19890057
2006 Transplantation of hNT neurons into the ischemic cortex: cell survival and effect on sensorimotor behavior. Journal of neuroscience research 57 16496370
2000 Intrastriatal and intranigral grafting of hNT neurons in the 6-OHDA rat model of Parkinson's disease. Experimental neurology 57 10739641
2005 Tumorigenicity issues of embryonic carcinoma-derived stem cells: relevance to surgical trials using NT2 and hNT neural cells. Stem cells and development 56 15725742
1997 Expression of tyrosine hydroxylase in newly differentiated neurons from a human cell line (hNT). Neuroreport 49 9172156
2020 Transcription Factor RREB1: from Target Genes towards Biological Functions. International journal of biological sciences 48 32210733
1999 Lithium chloride induces the expression of tyrosine hydroxylase in hNT neurons. Experimental neurology 48 10364437
2011 hZIP1 zinc transporter down-regulation in prostate cancer involves the overexpression of ras responsive element binding protein-1 (RREB-1). The Prostate 47 21360563
1989 Enteropathogenic Escherichia coli serotype O111:HNT isolated from preterm neonates in Nairobi, Kenya. Journal of clinical microbiology 45 2568996
2000 Dopaminergic phenotype of hNT cells in vitro. Brain research. Developmental brain research 44 10915908
2016 Comparison between PCL/hydroxyapatite (HA) and PCL/halloysite nanotube (HNT) composite scaffolds prepared by co-extrusion and gas foaming. Materials science & engineering. C, Materials for biological applications 43 28024618
2010 Rapid microarray-based genotyping of enterohemorrhagic Escherichia coli serotype O156:H25/H-/Hnt isolates from cattle and clonal relationship analysis. Applied and environmental microbiology 42 20581183
2004 Spinal implantation of hNT neurons and neuronal precursors: graft survival and functional effects in rats with ischemic spastic paraplegia. The European journal of neuroscience 42 15525281
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
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
2011 Patterning and detailed study of human hNT astrocytes on parylene-C/silicon dioxide substrates to the single cell level. Biomaterials 36 21641029
1996 Flupirtine increases the levels of glutathione and Bc1-2 in hNT (human Ntera/D1) neurons: mode of action of the drug-mediated anti-apoptotic effect. European journal of pharmacology 36 8982732
1998 Trophic effect of porcine Sertoli cells on rat and human ventral mesencephalic cells and hNT neurons in vitro. Cell transplantation 35 9588597
1997 Establishment of a novel human myeloid leukaemia cell line (HNT-34) with t(3;3)(q21;q26), t(9;22)(q34;q11) and the expression of EVI1 gene, P210 and P190 BCR/ABL chimaeric transcripts from a patient with AML after MDS with 3q21q26 syndrome. British journal of haematology 35 9266939
1997 Transforming growth factor-beta protects human hNT cells from degeneration induced by beta-amyloid peptide: involvement of the TGF-beta type II receptor. Brain research. Molecular brain research 35 9332729
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 33 37596700
2020 Fabrication of biocompatible antibacterial nanowafers based on HNT/PVA nanocomposites loaded with minocycline for burn wound dressing. Materials science & engineering. C, Materials for biological applications 31 32204113
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
2000 In vitro and in vivo characterization of hNT neuron neurotransmitter phenotypes. Brain research bulletin 30 11113579
2001 Intraspinal implantation of hNT neurons into SOD1 mice with apparent motor deficit. Amyotrophic lateral sclerosis and other motor neuron disorders : official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases 28 11958728
2023 The U2AF65/circNCAPG/RREB1 feedback loop promotes malignant phenotypes of glioma stem cells through activating the TGF-β pathway. Cell death & disease 27 36635261
2021 miR-26a enhances colorectal cancer cell growth by targeting RREB1 deacetylation to activate AKT-mediated glycolysis. Cancer letters 27 34419497
2020 Layered biocompatible pH-responsive antibacterial composite film based on HNT/PLGA/chitosan for controlled release of minocycline as burn wound dressing. International journal of biological macromolecules 27 32891643
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
2003 Differential connexin expression, gap junction intercellular coupling, and hemichannel formation in NT2/D1 human neural progenitors and terminally differentiated hNT neurons. Journal of neuroscience research 26 12692906
2010 First human hNT neurons patterned on parylene-C/silicon dioxide substrates: Combining an accessible cell line and robust patterning technology for the study of the pathological adult human brain. Journal of neuroscience methods 25 20933004
2000 The properties of hNT cells following transplantation into the subventricular zone of the neonatal forebrain. Experimental neurology 24 10785441
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
2004 Transplanted hNT cells ("LBS neurons") in a rat model of huntington's disease: good survival, incomplete differentiation, and limited functional recovery. Cell transplantation 19 15129758
2018 Sleeping Beauty Screen Identifies RREB1 and Other Genetic Drivers in Human B-cell Lymphoma. Molecular cancer research : MCR 18 30355676
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 18 24348900
2006 Multiple transplants of hNT cells into the spinal cord of SOD1 mouse model of familial amyotrophic lateral sclerosis. Amyotrophic lateral sclerosis : official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases 17 17127560
2001 Comparison of calcium-binding proteins expressed in cultured hNT neurons and hNT neurons transplanted into the rat striatum. Experimental neurology 17 11161613
2020 Mesenchymal tumours with RREB1-MRTFB fusion involving the mediastinum: extra-glossal ectomesenchymal chondromyxoid tumours? Histopathology 16 31991003
2002 Lithium exposure enhances survival of NT2N cells (hNT neurons) in the hemiparkinsonian rat. The European journal of neuroscience 15 12492421
2003 The transcription factor Nurr1 in human NT2 cells and hNT neurons. Brain research. Developmental brain research 14 14519498
2002 The Ginkgo biloba extract EGb 761 increases viability of hnt human neurons in culture and affectsthe expression of genes implicated in the stress response. Cellular and molecular biology (Noisy-le-Grand, France) 14 12396074
2000 Reduced pteridine derivatives induce apoptosis in human neuronal NT2/HNT cells. Immunobiology 14 10776802
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
2020 Effect of SrR delivery in the biomarkers of bone regeneration during the in vitro degradation of HNT/GN coatings prepared by EPD. Colloids and surfaces. B, Biointerfaces 13 32155456
2021 The transcription factor Rreb1 regulates epithelial architecture, invasiveness, and vasculogenesis in early mouse embryos. eLife 12 33929320
2014 Enrichment of differentiated hNT neurons and subsequent analysis using flow-cytometry and xCELLigence sensing. Journal of neuroscience methods 12 24530700
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
2001 In vitro induction and in vivo expression of bcl-2 in the hNT neurons. Brain research bulletin 12 11704352
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
2002 Nicotinic acetylcholine receptors on NT2 precursor cells and hNT (NT2-N) neurons. Brain research. Developmental brain research 11 12414096
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 9 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
2005 Long distance selective fiber outgrowth of transplanted hNT neurons in white matter tracts of the adult rat brain. The Journal of comparative neurology 9 15846787
2024 RREB1-mediated SUMOylation enhancement promotes chemoresistance partially by transcriptionally upregulating UBC9 in colorectal cancer. Frontiers in pharmacology 8 39108750
2017 Nanosecond UV lasers stimulate transient Ca2+ elevations in human hNT astrocytes. Journal of neural engineering 8 28291741
2000 The effects of taurine on hNT neurons transplanted in adult rat striatum. Cell transplantation 8 11202562
1998 The hNT human neuronal cell line survives and migrates into rat retina. Cell transplantation 8 9853583
1998 The study and application of biomimic peroxidase ferric 2-hydroxy-1-naphthaldehyde thiosemicarbazone (Fe(III)-HNT). Talanta 7 18967337
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
2002 CCK processing by pituitary GH3 cells, human teratocarcinoma cells NT2 and hNT differentiated human neuronal cells evidence for a differentiation-induced change in enzyme expression and pro CCK processing. Life sciences 6 11883703
2001 Apoptosis in cultured hNT neurons. Brain research. Developmental brain research 6 11287065
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 5 39991628
2022 Ras signaling and RREB1 are required for the dissociation of medial edge epithelial cells in murine palatogenesis. Disease models & mechanisms 5 34897389
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 5 36325821
2019 Large 10  ×  10 single cell grid networks of human hNT astrocytes on raised parylene-C/SiO2 substrates. Journal of neural engineering 5 31394515
2005 Over-expression of p73beta results in apoptotic death of post-mitotic hNT neurons. Journal of the neurological sciences 5 16212980
2004 Intraspinal transplantation of hNT neurons in the lesioned adult rat spinal cord. The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 5 15038476
2021 Regulatory SNP of RREB1 is Associated With Bone Mineral Density in Chinese Postmenopausal Osteoporosis Patients. Frontiers in genetics 4 34868232
2025 Evaluation of the effects of cartilage decellularized ECM in optimizing PHB-chitosan-HNT/chitosan-ECM core-shell electrospun scaffold: Physicochemical and biological properties. Biomaterials advances 3 40048901
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
2024 The first case of a point pathogenic variant in the RREB1 gene in Noonan-like Rasopathy. Clinical genetics 2 38332451
2022 Critical Spatial-Temporal Dynamics and Prominent Shape Collapse of Calcium Waves Observed in Human hNT Astrocytes in Vitro. Frontiers in physiology 2 35784870
2021 Knockdown of RREB1 inhibits cell proliferation via enhanced p16 expression in gastric cancer. Cell cycle (Georgetown, Tex.) 2 34666611
2013 A Cell Derived Active Contour (CDAC) method for robust tracking in low frame rate, low contrast phase microscopy - an example: the human hNT astrocyte. PloS one 2 24358233