Affinage

MLXIPL

Carbohydrate-responsive element-binding protein · UniProt Q9NP71

Length
852 aa
Mass
93.1 kDa
Annotated
2026-06-10
100 papers in source corpus 45 papers cited in narrative 45 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MLXIPL (ChREBP) is a glucose-responsive basic helix-loop-helix-leucine zipper transcription factor that couples cellular carbohydrate flux to the transcriptional control of glycolytic and lipogenic gene programs across liver, adipose, intestine, pancreatic β-cells, and kidney (PMID:11230181, PMID:12087089, PMID:18292813). It functions as an obligate heterodimer with Mlx, binding E-box/carbohydrate response element (ChoRE) sequences in target promoters such as L-PK and Glut5 (PMID:11230181, PMID:12087089, PMID:29263303). Its activity is governed by glucose-flux-driven nucleocytoplasmic shuttling: xylulose-5-phosphate activates PP2A to dephosphorylate ChREBP and permit nuclear entry, while polyunsaturated fatty acids suppress activity by lowering xylulose-5-phosphate and blocking nuclear translocation (PMID:16890538, PMID:18490833, PMID:16184193). Subcellular distribution is set by a competition at the N-terminal regulatory domain in which phosphorylation promotes 14-3-3 binding and CRM1-dependent export, whereas the dephosphorylated form engages importin-α at a bipartite NLS for nuclear import (PMID:18606808, PMID:21665952, PMID:23086940). Site-specific O-GlcNAcylation, enabled by OGT recruited through glucose-dependent O-GlcNAcylated HCF-1, stabilizes ChREBP and enhances Mlx heterodimerization and DNA binding, with HCF-1 also recruiting PHF2 for epigenetic activation of lipogenic promoters (PMID:21471514, PMID:31227231, PMID:28450420). Protein abundance is additionally controlled by SMURF2-mediated ubiquitination and by KCTD17, which raises O-GlcNAcylated ChREBP by destabilizing OGA (PMID:31409643, PMID:36402191). A constitutively active isoform, ChREBP-β, lacking the N-terminal inhibitory domain, is induced from an alternative promoter downstream of glucose-activated ChREBP-α and drives adipose de novo lipogenesis and systemic insulin sensitivity (PMID:22466288). In the nucleus ChREBP cooperates with c-Myc and PPARα to activate glucose-responsive and FGF21 genes and is restrained by SIRT6 deacetylation (PMID:20382893, PMID:29020627, PMID:34425214). Beyond lipogenesis, ChREBP governs fructose handling via GLUT5 and the LPK/G6PC axes, drives a ChREBP–FGF21 feedforward loop, controls TXNIP, MTTP-dependent VLDL secretion, and mitochondrial lipid remodeling, and acts as an oncogenic driver of aerobic glycolysis and proliferation in hepatocellular and colorectal cancers (PMID:27669460, PMID:28123933, PMID:29263303, PMID:29518948, PMID:38424041, PMID:37611830).

Mechanistic history

Synthesis pass · year-by-year structured walk · 42 steps
  1. 2001 High

    Established the core molecular identity of ChREBP as a bHLH-leucine zipper factor that heterodimerizes with Mlx to bind E-box DNA, defining the obligate partnership underlying all downstream activity.

    Evidence Co-immunoprecipitation, EMSA, and reporter assays demonstrating Mlx heterodimerization and CACGTG binding

    PMID:11230181

    Open questions at the time
    • Initial study reported E-box repression rather than the activation later shown at ChoREs
    • Did not define glucose-responsiveness mechanism
  2. 2002 High

    Showed ChREBP is glucose-regulated in pancreatic islet cells and binds the L-PK promoter in a glucose-dependent manner, linking the factor to a physiological metabolic readout.

    Evidence Nuclear run-on, inducible overexpression, and EMSA in INS-1 cells and rat islets

    PMID:12087089

    Open questions at the time
    • Did not define the upstream glucose-sensing biochemistry
    • Mechanism of nuclear translocation not addressed
  3. 2006 High

    Defined the upstream metabolic signal activating ChREBP, identifying xylulose-5-phosphate/PP2A-mediated dephosphorylation as the switch enabling nuclear import.

    Evidence Biochemical pathway reconstitution, PP2A activity assays, and nuclear fractionation in hepatocytes

    PMID:16890538 PMID:18490833

    Open questions at the time
    • Precise phosphosites controlled by PP2A not fully mapped here
    • Did not address competing import/export machinery
  4. 2005 High

    Identified PUFAs as physiological inhibitors acting through reduced xylulose-5-phosphate and blocked nuclear translocation, defining nutrient-specific negative regulation independent of AMPK.

    Evidence Mouse hepatocyte in vivo/in vitro studies, AMPK-KO controls, and constitutively nuclear isoform rescue

    PMID:16184193

    Open questions at the time
    • Did not resolve direct lipid sensing vs. purely metabolite-mediated effects
  5. 2008 High

    Resolved the molecular basis of cytoplasmic retention versus nuclear import as a phosphorylation-dependent competition between 14-3-3 and importin-α at the N-terminal regulatory domain.

    Evidence Synthetic peptide binding, isothermal titration calorimetry, mutagenesis, and nuclear fractionation

    PMID:18606808

    Open questions at the time
    • Did not yet provide structural detail of the 14-3-3 interface
    • Kinases responsible for specific phosphosites not all defined
  6. 2008 High

    Established genetic epistasis placing ChREBP, not LXR, as the essential transducer of glucose-induced lipogenic gene expression in liver.

    Evidence LXRα/β knockout mice, ChREBP siRNA, FRET, and nuclear fractionation

    PMID:18292813

    Open questions at the time
    • Did not exclude LXR contributions under other conditions
  7. 2010 High

    Defined a cofactor requirement, showing c-Myc is needed for glucose-stimulated co-recruitment of ChREBP and the transcriptional machinery to the Pklr promoter.

    Evidence Time-course ChIP, nuclear run-on, and small-molecule c-Myc inhibition

    PMID:20382893

    Open questions at the time
    • Order of recruitment vs. direct interaction not fully resolved
    • Generality across other ChoRE genes not tested
  8. 2011 High

    Mapped the bipartite NLS bound by importin-α and a competing secondary 14-3-3 site, mechanistically detailing the nuclear import determinants required for glucose-stimulated activity.

    Evidence Site-directed mutagenesis (K159A, K190A), binding assays, and transcriptional reporters

    PMID:21665952

    Open questions at the time
    • In vivo contribution of individual residues not tested in animals
  9. 2011 High

    Identified O-GlcNAcylation as a glucose-coupled modification that stabilizes ChREBP and enhances its lipogenic transcriptional output, linking nutrient flux to protein stability.

    Evidence Reciprocal Co-IP with OGT and in vivo adenoviral OGT/OGA gain/loss-of-function in mouse liver

    PMID:21471514

    Open questions at the time
    • Specific O-GlcNAc sites not mapped in this study
    • Interplay with phosphorylation not yet defined
  10. 2011 Medium

    Extended the regulatory network by showing ChREBP transcriptionally represses SIRT1 in the fed state, positioning it within nutrient-sensitive deacetylase signaling.

    Evidence ChREBP-KO mice, ChIP, and reporter assays across nutritional states

    PMID:21836635

    Open questions at the time
    • Direct vs. indirect repression not fully dissected
    • Single-lab finding
  11. 2011 Medium

    Demonstrated ChREBP mediates glucose repression of PPARα in β-cells, broadening its role beyond gene activation to nutrient-dependent gene silencing.

    Evidence Constitutively active ChREBP and siRNA knockdown in insulinoma cells and islets

    PMID:21282101

    Open questions at the time
    • Direct promoter binding not definitively shown
    • Single-lab finding
  12. 2012 High

    Discovered the constitutively active ChREBP-β isoform induced by ChREBP-α from an alternative promoter, revealing a feedforward amplification mechanism driving adipose lipogenesis and insulin sensitivity.

    Evidence 5'-RACE promoter mapping, adenoviral and siRNA manipulation in adipocytes, and GLUT4-KO mouse model

    PMID:22466288

    Open questions at the time
    • Regulation of ChREBP-β promoter choice not fully defined
    • Tissue-specific control of isoform balance unresolved
  13. 2012 High

    Provided the crystal structure of 14-3-3β bound to the ChREBP N-terminal regulatory helix, revealing a novel phosphorylation-independent binding mode for cytoplasmic retention.

    Evidence X-ray crystallography at 2.4 Å with structure-based mutagenesis

    PMID:23086940

    Open questions at the time
    • Reconciliation with phosphorylation-dependent 14-3-3 binding at other sites not fully integrated
  14. 2012 High

    Established ChREBP as a driver of glucose-stimulated β-cell proliferation through cell-cycle gene induction, connecting metabolic sensing to proliferative control.

    Evidence ChREBP-KO, siRNA, and adenoviral overexpression in β-cell systems with proliferation readouts

    PMID:22586588

    Open questions at the time
    • Direct cyclin promoter targets not mapped
    • Relationship to mitogenic ChREBP role in other tissues unclear
  15. 2009 High

    Linked ChREBP to proliferation and tumor growth, showing its loss redirects glucose metabolism toward oxidative phosphorylation and activates p53-dependent arrest.

    Evidence RNAi knockdown, metabolic flux analysis, p53 reporters, and xenograft tumor model

    PMID:19995986

    Open questions at the time
    • Mechanism connecting ChREBP loss to p53 activation not defined
    • Direct vs. metabolic indirect effect on proliferation unresolved
  16. 2013 High

    Demonstrated evolutionary conservation of the Mondo/Mlx network in dietary sugar tolerance and showed glycolytic, not lipogenic, targets are the critical effectors in Drosophila.

    Evidence Genetic null mutants, systematic RNAi screen, lipidomics, and metabolite measurements

    PMID:23593032

    Open questions at the time
    • Direct translation of dispensable lipogenesis to mammals not established
  17. 2013 Medium

    Identified FLII as a direct interactor that negatively regulates ChREBP via its DNA-binding domain, adding an actin-remodeling protein to the repressor set in cancer cells.

    Evidence Proteomic pulldown, Co-IP, domain mapping, and FLII gain/loss-of-function

    PMID:24055811

    Open questions at the time
    • Physiological context of FLII regulation not established
    • Single-lab finding
  18. 2008 Medium

    Defined a negative feedback loop in which ChREBP induces BHLHB2/DEC1, which in turn represses ChREBP lipogenic targets, providing autoregulatory damping of lipogenesis.

    Evidence Promoter deletion, ChIP, and dominant-active ChREBP overexpression in rat hepatocytes

    PMID:18602890

    Open questions at the time
    • In vivo physiological relevance not established
    • Single-lab finding
  19. 2015 Medium

    Showed ChREBP controls PPARγ activity and adipocyte differentiation in a FASN-dependent manner, implicating ChREBP-driven lipid ligand generation in nuclear receptor activation.

    Evidence Constitutively active/dominant-negative ChREBP, siRNA, PPARγ LBD reporter, and FASN inhibition

    PMID:26181104

    Open questions at the time
    • The endogenous FASN-derived ligand not identified
    • Mechanism inferred indirectly
  20. 2016 High

    Established ChREBP as the dominant transducer of fructose-induced glycolytic, lipogenic, and gluconeogenic gene expression, including a G6PC axis controlling hepatic glucose production independent of FoxO1.

    Evidence ChREBP-KO and FoxO1-KO epistasis, hexose-phosphate measurements, G6PC activity assays, and human validation

    PMID:27669460

    Open questions at the time
    • Sensing of fructose-derived hexose-phosphates not mechanistically resolved
  21. 2016 High

    Identified ChREBP as required for fructose-induced FGF21 secretion and revealed a FGF21→ChREBP-β feedforward loop coupling lipogenesis to endocrine signaling.

    Evidence ChREBP-KO and FGF21-KO mice, plasma FGF21 ELISA, and isotope tracer lipogenesis measurements

    PMID:28123933

    Open questions at the time
    • Molecular route of FGF21 feedback onto ChREBP-β not defined
  22. 2016 Medium

    Placed mTORC2 upstream of ChREBP-β in white adipose tissue, linking nutrient-sensitive kinase signaling to adipose lipogenesis and hepatic insulin sensitivity.

    Evidence Adipocyte-specific Rictor-KO mice with lipogenic and insulin-sensitivity phenotyping

    PMID:27098609

    Open questions at the time
    • Direct vs. glucose-uptake-mediated control of ChREBP-β not fully separated
  23. 2017 High

    Mapped functional O-GlcNAc sites (Ser839, Ser614) and showed Ser839 modification is essential for Mlx heterodimerization, DNA binding, and CRM1/14-3-3-mediated export, integrating glycosylation with phosphorylation crosstalk.

    Evidence Chemoenzymatic and metabolic labeling, mass spectrometry, mutagenesis, Co-IP, and DNA-binding assays

    PMID:28450420

    Open questions at the time
    • In vivo physiological impact of individual sites not tested
  24. 2017 High

    Identified PPARα as a required partner establishing chromatin accessibility for ChREBP binding at the Fgf21 ChoRE, defining a cooperative cofactor mechanism for glucose-induced FGF21.

    Evidence ChREBP-KO and PPARα-KO mice, ChIP, ATAC-seq, and ChREBP re-expression rescue

    PMID:29020627

    Open questions at the time
    • Whether PPARα acts at other ChREBP targets not addressed
  25. 2017 Medium

    Showed mTOR associates with the ChREBP-Mlx complex in β-cells and restrains TXNIP expression, identifying a kinase-complex interaction modulating oxidative stress.

    Evidence Co-IP and β-cell-specific mTOR-KO mice with TXNIP and oxidative stress readouts

    PMID:28606928

    Open questions at the time
    • Direct phosphorylation of complex components not shown
    • Single-lab finding
  26. 2017 Medium

    Positioned retinol saturase (RetSat) as a non-catalytic upstream activator of hepatic ChREBP, expanding the set of upstream regulators of lipogenic ChREBP activity.

    Evidence Liver-specific RetSat depletion with ChREBP rescue and dihydroretinol supplementation

    PMID:28855500

    Open questions at the time
    • Biochemical mechanism of RetSat→ChREBP connection undefined
  27. 2017 High

    Established intestinal ChREBP as a direct activator of the Glut5 fructose transporter, demonstrating tissue-specific control of fructose absorption distinct from hepatic functions.

    Evidence Intestine- and liver-specific ChREBP-KO mice, Glut5 promoter ChIP, and Caco-2BBE transactivation assays

    PMID:29263303

    Open questions at the time
    • Regulation of intestinal ChREBP isoform balance not addressed
  28. 2018 Medium

    Confirmed direct ChREBP/Mlx activation of the Glut5 ChoRE in intestine with target specificity, reinforcing the fructose-malabsorption phenotype of ChREBP loss.

    Evidence ChIP on Glut5 vs. NHE3 promoters and Caco-2BBE reporter assays in ChREBP-KO mice

    PMID:29669261

    Open questions at the time
    • Single-lab finding overlapping prior intestinal study
  29. 2018 High

    Defined the ChREBP–SREBP-1c division of labor in postprandial lipogenesis, showing ChREBP mediates glucose induction and supports SREBP-1c levels in the fed state.

    Evidence Liver-specific ChREBP-KO, AAV nuclear SREBP-1c restoration, and Scap-deficient mice

    PMID:29335275

    Open questions at the time
    • Direct physical interaction between the two factors not established
  30. 2018 Medium

    Identified MTTP as the principal ChREBP target governing hepatic VLDL secretion, linking ChREBP to lipoprotein export.

    Evidence Adenoviral ChREBP/SHP, promoter reporters, and Chrebp/Shp single and double KO mice with VLDL secretion rates

    PMID:29518948

    Open questions at the time
    • Direct ChoRE in Mttp promoter not definitively mapped
    • Single-lab finding
  31. 2018 Medium

    Showed ChREBP and Myc cooperatively program hepatocyte proliferation and metabolism, with distinct and shared transcriptional outputs including ribosomal genes.

    Evidence Chrebp and Myc single/double KO mice, hepatoblastoma models, RNA-Seq, and metabolic flux studies

    PMID:30087120

    Open questions at the time
    • Whether cooperation reflects direct co-binding not established
    • Single-lab finding
  32. 2019 High

    Defined HCF-1 as a glucose-sensitive cofactor that, after its own O-GlcNAcylation, recruits OGT to ChREBP and PHF2 for epigenetic activation at lipogenic promoters, mechanistically linking glucose to chromatin modification.

    Evidence Co-IP, ChIP, O-GlcNAc site mapping, knockdown, and histone modification assays

    PMID:31227231

    Open questions at the time
    • Generality across non-lipogenic ChREBP targets not tested
  33. 2019 Medium

    Identified SMURF2 as the E3 ligase driving ChREBP ubiquitination and degradation, with AKT acting upstream, defining a degradation arm controlling ChREBP-dependent glycolysis in cancer.

    Evidence Co-IP, ubiquitination assays, SMURF2 gain/loss-of-function, and AKT inhibition in colorectal cancer cells

    PMID:31409643

    Open questions at the time
    • Ubiquitination site on ChREBP not mapped
    • Single-lab finding
  34. 2020 High

    Revealed a protective hepatic function in which ChREBP-driven LPK channels glucose-6-phosphate away from glycogen, preventing fructose-induced glycogenic hepatotoxicity.

    Evidence Liver-specific ChREBP-KO with high-fructose diet and hepatic LPK overexpression rescue

    PMID:31974143

    Open questions at the time
    • Mechanism of G6P partitioning beyond LPK not addressed
  35. 2021 Medium

    Established SIRT6 as a direct negative regulator that deacetylates and suppresses ChREBP, restraining lipogenic gene expression.

    Evidence Co-IP, deacetylation assays, and SIRT6 liver-specific KO mice with Western-diet phenotyping

    PMID:34425214

    Open questions at the time
    • Specific deacetylated lysines not mapped
    • Single-lab finding
  36. 2021 Medium

    Defined a dual ChREBP/FoxO1 regulation of hepatic TXNIP across fed and fasted states, establishing nutrient-state-specific control of a shared target.

    Evidence ChREBP-KO and FoxO1-KO mice with ChIP-qPCR and reporter assays

    PMID:33748706

    Open questions at the time
    • Mechanism of state-specific switching between the two factors unresolved
  37. 2021 Medium

    Placed ChREBP downstream of thyroid hormone receptor TRβ1 in driving hepatic lipogenesis, showing TH regulates ChREBP activation and DNA recruitment.

    Evidence Hepatocyte-specific TRβ1-KO and ChREBP-KO mice, T3 treatment, ChREBP ChIP, and human iPSC-hepatocyte validation

    PMID:34784250

    Open questions at the time
    • Direct vs. indirect TH-mediated ChREBP activation not fully defined
  38. 2022 High

    Identified KCTD17 as a stabilizer of ChREBP that acts by promoting OGA degradation to elevate ChREBP O-GlcNAcylation, integrating the SREBP1c–KCTD17 axis with ChREBP stability in obesity.

    Evidence CRISPR hepatocyte-specific single and double KO (Kctd17, Oga), AAV delivery, and HFD metabolic phenotyping

    PMID:36402191

    Open questions at the time
    • Direct KCTD17–OGA mechanism vs. broader effects not fully separated
  39. 2022 Medium

    Demonstrated direct small-molecule targeting of ChREBP by celastrol, which blocks nuclear translocation and promotes degradation to repress TXNIP and ameliorate diabetes, providing pharmacological validation of ChREBP as a target.

    Evidence Molecular docking, CETSA, DARTS, mass spectrometry, nuclear fractionation, and db/db mouse model

    PMID:36603341

    Open questions at the time
    • Binding site on ChREBP not defined
    • Selectivity vs. other targets not established
  40. 2023 Medium

    Identified a ChREBP target (HGFAC) connecting glucose-sensing transcription to systemic lipid and glucose homeostasis via hepatic PPARγ, with concordance between mouse and human genetics.

    Evidence ChREBP ChIP-Seq integrated with human GWAS and HGFAC gain/loss-of-function mouse models

    PMID:36413406

    Open questions at the time
    • PPARγ activation mechanism partially inferred
    • Single-lab finding
  41. 2023 Medium

    Linked ChREBP to mitochondrial morphology in kidney podocytes through transcriptional activation of Gnpat and ether phospholipid synthesis, extending its remit to organelle remodeling in diabetic nephropathy.

    Evidence Inducible podocyte-specific ChREBP knockdown in db/db mice, lipidomics, ChIP, GNPAT rescue, and EM

    PMID:37611830

    Open questions at the time
    • Generality of ether-lipid mechanism to other tissues unknown
    • Single-lab finding
  42. 2024 High

    Defined ChREBP as an oncogenic driver in hepatocellular carcinoma that sustains PI3K/AKT signaling via p85α and reroutes glucose/glutamine flux, with pharmacological inhibition suppressing tumor growth.

    Evidence ChREBP loss-of-function, ChIP-Seq, metabolic flux analysis, p85α promoter assays, and SBI-993 in vivo xenografts

    PMID:38424041

    Open questions at the time
    • Therapeutic window and selectivity of inhibition not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple regulatory layers — phosphorylation, O-GlcNAcylation, acetylation, 14-3-3/importin shuttling, ubiquitination, and cofactor recruitment — are integrated in real time to set ChREBP output in a tissue- and nutrient-specific manner remains unresolved.
  • No unified quantitative model linking PTM crosstalk to transcriptional output
  • Tissue-specific isoform and cofactor balance not systematically mapped
  • Structural basis of full-length ChREBP-Mlx ChoRE engagement undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 4
Pathway
R-HSA-1430728 Metabolism 6 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-8953897 Cellular responses to stimuli 3
Partners
HCFC1LIPEMLXMYCOGTSIRT6SMURF2YWHAB
Complex memberships
ChREBP-Mlx heterodimer

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 WBSCR14 (MLXIPL/ChREBP) encodes a bHLH-leucine zipper transcription factor that heterodimerizes with Mlx to bind the DNA sequence CACGTG (E-box); association with Mlx represses E-box-dependent transcription, analogous to Mad/Max interactions. Heterodimer formation and DNA-binding demonstrated by co-immunoprecipitation and electrophoretic mobility shift assay (EMSA); transcriptional repression confirmed by reporter assay Human molecular genetics High 11230181
2006 ChREBP is activated by increased glucose flux: xylulose 5-phosphate (generated via the pentose phosphate pathway) triggers protein phosphatase 2A (PP2A), which dephosphorylates ChREBP, enabling its nuclear import and transcriptional activation of glycolytic and lipogenic genes. Biochemical pathway reconstitution; measurement of xylulose 5-phosphate levels; PP2A activity assays; nuclear fractionation in hepatocytes Cell metabolism High 16890538 18490833
2005 Polyunsaturated fatty acids (PUFAs: C18:2, C20:5, C22:6) suppress ChREBP activity by increasing ChREBP mRNA decay and blocking its nuclear translocation (independently of AMPK), whereas saturated and monounsaturated fatty acids have no effect. The PUFA-mediated inhibition is primarily through reduction of xylulose 5-phosphate concentrations. In vivo and in vitro mouse hepatocyte experiments; nuclear fractionation; AMPK-knockout hepatocytes; overexpression of constitutively nuclear ChREBP isoform to rescue PUFA inhibition The Journal of clinical investigation High 16184193
2008 ChREBP nuclear export is regulated by phosphorylation-dependent binding to 14-3-3 proteins: 14-3-3 binds an α-helix (residues 125–135) of the N-terminal domain of ChREBP, facilitated by phosphorylation of nearby Ser-140 and Ser-196. Phosphorylation also enables CRM1-mediated nuclear export, whereas dephosphorylated ChREBP interacts with importin-α for nuclear import; 14-3-3 and importin-α compete for ChREBP binding. In vitro binding assays with synthetic peptides; isothermal titration calorimetry (Kd = 1.1 µM for phospho-Ser-140 peptide); fluorescence spectroscopy; site-directed mutagenesis; nuclear fractionation The Journal of biological chemistry High 18606808
2011 ChREBP is O-GlcNAcylated in liver cells through interaction with O-GlcNAc transferase (OGT). O-GlcNAcylation stabilizes the ChREBP protein and increases its transcriptional activity toward glycolytic (L-PK) and lipogenic (ACC, FAS, SCD1) target genes in combination with active glucose flux. OGT overexpression increases nuclear ChREBP O-GlcNAc levels and promotes hepatic lipogenesis; OGA overexpression reduces lipogenic protein content and prevents hepatic steatosis in db/db mice. Co-immunoprecipitation of ChREBP with OGT; adenoviral overexpression/inhibition of OGT and OGA in mouse hepatocytes and in vivo; immunoblot for nuclear ChREBP-OGlcNAc Diabetes High 21471514
2011 ChREBP imports into the nucleus via a classical bipartite nuclear localization signal (NLS) spanning residues 158–190; importin-α binds this NLS, and replacing Lys-159/Lys-190 with alanine abolishes importin-α binding, glucose-stimulated transcriptional activity, and nuclear localization. A secondary 14-3-3 binding site (α3 helix, residues 170–190, phospho-Ser-196) competes with importin-α. In vitro binding assays; site-directed mutagenesis (K159A, K190A); nuclear localization assays; transcriptional reporter assays The Journal of biological chemistry High 21665952
2012 Crystal structure of 14-3-3β bound to the N-terminal regulatory region of ChREBP at 2.4 Å resolution reveals that ChREBP α2 helix (residues 117–137) binds 14-3-3 in a phosphorylation-independent, novel mode distinct from all previously characterized 14-3-3 interactions; structure-based mutagenesis disrupting this interface abolishes complex formation. X-ray crystallography (2.4 Å); structure-based mutagenesis; in vitro binding assays The Journal of biological chemistry High 23086940
2008 ChREBP, but not liver X receptors (LXRs), is required for glucose-induced expression of L-PK, ACC, and FAS in mouse liver. LXR stimulation did not promote ChREBP nuclear localization in the absence of increased intrahepatic glucose flux; glucose induction of these genes was identical in LXRα/β knockout vs. wild-type mice; siRNA silencing of ChREBP in LXRα/β-KO hepatocytes abrogated glucose-induced L-PK and ACC expression. LXR knockout mice; LXR agonist treatment; siRNA knockdown of ChREBP; FRET analysis of LXR-cofactor interactions; nuclear fractionation The Journal of clinical investigation High 18292813
2012 ChREBP mediates glucose-stimulated pancreatic β-cell proliferation; depletion of ChREBP decreases glucose-stimulated proliferation and cell-cycle accelerator expression, while overexpression amplifies glucose-stimulated proliferation with increases in cyclin gene expression. ChREBP knockout mouse β-cells; siRNA knockdown in INS-1 832/13 cells and primary rat/human β-cells; adenoviral overexpression; BrdU/[3H]thymidine incorporation; FACS; qRT-PCR Diabetes High 22586588
2012 A novel, potent ChREBP isoform (ChREBP-β) is transcribed from an alternative promoter in adipose tissue; glucose-mediated activation of canonical ChREBP-α induces ChREBP-β expression. ChREBP-β lacks the N-terminal inhibitory LID domain and is constitutively active. Adipose ChREBP-β is a major determinant of adipose tissue de novo lipogenesis and systemic insulin sensitivity. Identification of alternative promoter by 5′-RACE; adenoviral overexpression and siRNA knockdown in adipocytes; GLUT4-knockout mouse model; measurement of lipogenic rates Nature High 22466288
2019 Host cell factor 1 (HCF-1) is a ChREBP-interacting protein; HCF-1 must first be O-GlcNAcylated in response to glucose to bind ChREBP, after which it recruits OGT to O-GlcNAcylate and activate ChREBP. The HCF-1:ChREBP complex occupies lipogenic gene promoters where HCF-1 regulates H3K4 trimethylation and recruits the histone demethylase PHF2 for epigenetic activation. Co-immunoprecipitation; ChIP at lipogenic gene promoters; O-GlcNAc site mapping; genetic knockdown; histone modification assays Molecular cell High 31227231
2017 Site-specific O-GlcNAcylation of ChREBP: Ser839 O-GlcNAcylation is essential for Mlx heterodimerization and enhanced DNA-binding activity, and is also crucial for ChREBP nuclear export via strengthening interactions with CRM1 and 14-3-3. Ser614 O-GlcNAcylation was identified by mass spectrometry. Ser514 phosphorylation under high glucose conditions enhances subsequent O-GlcNAcylation of ChREBP. Chemoenzymatic labeling; metabolic labeling; mass spectrometry; site-directed mutagenesis; co-immunoprecipitation; DNA-binding assays Molecular & cellular proteomics High 28450420
2010 c-Myc is required for ChREBP-dependent activation of glucose-responsive genes; glucose promotes co-recruitment of both ChREBP and c-Myc to the Pklr promoter. Depletion of c-Myc activity abolishes glucose-mediated recruitment of HNF4α, ChREBP, and RNA Pol II without affecting basal expression, constitutively bound HNF1α, or histone acetylation. Time-course chromatin immunoprecipitation (ChIP); nuclear run-on transcription assay; small molecule inhibition of c-Myc (10058-F4); reporter assays Molecular endocrinology High 20382893
2002 ChREBP (WBSCR14/MLXIPL) is present in rat islets and INS-1 cells; glucose stimulates ChREBP transcription (nuclear run-on); overexpression of ChREBP in INS-1 cells produces a left shift in glucose responsiveness of L-PK expression and enhanced L-PK promoter activity; both endogenous and induced ChREBP bind the L-PK promoter in a glucose-dependent manner. Nuclear run-on experiment; tet-on inducible overexpression system; Northern/Western blot; EMSA (L-PK promoter binding); immunofluorescence The Journal of biological chemistry High 12087089
2009 ChREBP expression is induced by mitogenic stimulation and is required for efficient cell proliferation. Suppression of ChREBP redirects glucose metabolism from aerobic glycolysis/lipogenesis/nucleotide biosynthesis toward oxidative phosphorylation, activates p53, and causes cell cycle arrest. In vivo, ChREBP suppression leads to p53-dependent reduction in tumor growth. RNAi-mediated knockdown; metabolic flux measurements; p53 reporter assays; in vivo xenograft tumor model PNAS High 19995986
2013 In Drosophila, the Mondo (ChREBP ortholog)/Mlx transcriptional network is essential for dietary sugar tolerance; Mlx-null and mondo-reduced larvae have widespread changes in lipid and phospholipid profiles, elevated circulating glucose, and markedly reduced survival on high-sugar diets. Systematic loss-of-function of Mlx target genes identifies Phosphofructokinase 2 (glycolysis), Cabut (KLF transcription factor), and Aldehyde dehydrogenase III as required for sugar tolerance, while fatty acid synthesis is not required and is in fact detrimental. Genetic null mutants; systematic RNAi loss-of-function screen; lipidomics; metabolite measurements PLoS genetics High 23593032
2011 ChREBP represses SIRT1 expression in the fed state (high nutrient availability); CREB activates SIRT1 expression during fasting. These opposing transcription factors control SIRT1 expression in a nutrient-sensitive manner across metabolic tissues. Genetic loss-of-function (ChREBP knockout); chromatin immunoprecipitation; reporter assays; metabolic tissue analysis in multiple nutritional states EMBO reports Medium 21836635
2016 ChREBP is activated by fructose-derived hexose-phosphates in liver and is required for fructose-induced induction of glycolytic, lipogenic, and gluconeogenic (G6pc) genes. ChREBP-driven G6PC activity is a major determinant of hepatic glucose production and reduces glucose-6-phosphate levels. This ChREBP/G6PC axis operates independently of FoxO1 and dominates over insulin suppression. ChREBP knockout mice; FoxO1-knockout epistasis; hepatic hexose-phosphate measurements; in vivo fructose gavage; G6PC activity assays; conservation confirmed in human cells The Journal of clinical investigation High 27669460
2017 ChREBP and PPARα cooperate to regulate glucose-induced FGF21 expression in the liver; PPARα is required for chromatin accessibility at the Fgf21 promoter and for ChREBP binding to the Fgf21 ChoRE. Hepatic PPARα knockout reduces glucose-mediated FGF21 induction, which is restored by active ChREBP re-expression. ChREBP-KO and PPARα-KO mice; adenoviral ChREBP re-expression; microarray; ChIP for ChREBP at Fgf21 ChoRE; ATAC-seq/chromatin accessibility Cell reports High 29020627
2016 ChREBP is required for fructose-induced FGF21 secretion; in ChREBP-KO mice, the acute rise in circulating FGF21 following fructose gavage is absent. FGF21 in turn amplifies ChREBP-β and its lipogenic/fructolytic gene targets, constituting a ChREBP–FGF21 feedforward signaling axis. ChREBP-KO mice; FGF21-KO mice; fructose gavage; plasma FGF21 ELISA; stable isotope tracer de novo lipogenesis measurements Molecular metabolism High 28123933
2017 Intestinal ChREBP directly binds the Glut5 (Slc2a5) promoter and transcriptionally activates GLUT5 expression; ChREBP and its partner Mlx co-activate the Glut5 promoter. Intestine-specific ChREBP KO leads to fructose intolerance with downregulation of GLUT5 and fructolytic genes, while liver-specific KO does not impair fructose tolerance. Tissue-specific ChREBP knockout mice (intestine and liver); ChIP on Glut5 promoter; transient transfection/promoter assay with ChREBP + Mlx in Caco-2BBE cells; high-fructose diet phenotyping JCI insight High 29263303
2018 Hormone-sensitive lipase (HSL) physically interacts with ChREBP-α (independently of lipase activity), impairing ChREBP-α nuclear translocation and induction of the constitutively active ChREBP-β isoform. Loss of HSL in adipocytes enhances ChREBP-α nuclear entry, drives ChREBP-β-dependent induction of ELOVL6, increases membrane oleic acid, and enhances insulin signaling. Co-immunoprecipitation of HSL and ChREBP; genetic inhibition of HSL in human adipocytes and mouse adipose; siRNA knockdown of ChREBP and ELOVL6; nuclear fractionation; phospholipid analysis Nature metabolism High 32694809
2018 ChREBP directly binds to the Glut5 promoter in intestinal cells (confirmed by ChIP) and, together with its heterodimer partner Mlx, activates Glut5 promoter activity. ChREBP KO mice exhibit sucrose intolerance and fructose malabsorption with suppression of fructose transport and metabolism gene expression. ChREBP KO mice; ChIP on Glut5 promoter in small intestine; co-transfection reporter assay in Caco-2BBE; RT-PCR; gut microbiota analysis Metabolism: clinical and experimental High 29669261
2008 BHLHB2/DEC1 constitutes a negative feedback loop with ChREBP in regulating lipogenesis: ChREBP induces Bhlhb2 expression via a functional ChoRE in the Bhlhb2 promoter, and BHLHB2 in turn inhibits ChREBP-mediated induction of Fasn and Lpk by binding to their ChoRE sequences. Promoter deletion analysis; ChIP assay for BHLHB2 binding to Fasn, Lpk, and Bhlhb2 promoters; overexpression of dominant-active ChREBP; RT-PCR in rat hepatocytes Biochemical and biophysical research communications Medium 18602890
2017 mTOR associates with the ChREBP-Mlx complex in pancreatic β-cells and inhibits ChREBP transcriptional activity, leading to decreased TXNIP expression. mTOR deficiency in β-cells increases ChREBP-Mlx-driven TXNIP expression and oxidative stress. Co-immunoprecipitation of mTOR with ChREBP-Mlx; β-cell-specific mTOR knockout mice; TXNIP expression analysis; oxidative stress markers The Journal of cell biology Medium 28606928
2021 SIRT6 physically interacts with ChREBP in hepatocytes and suppresses ChREBP transcriptional activity through direct deacetylation, thereby reducing lipogenic gene expression. SIRT6 liver-specific KO leads to elevated ChREBP protein levels and activity. Co-immunoprecipitation of SIRT6 with ChREBP; deacetylation assay; SIRT6 liver-specific KO mice; Western diet metabolic phenotyping Biochimica et biophysica acta. Molecular basis of disease Medium 34425214
2019 SMURF2 (E3 ubiquitin ligase) interacts with ChREBP and promotes its ubiquitination and proteasomal degradation. SMURF2 expression inversely correlates with ChREBP levels. AKT acts upstream to suppress SMURF2, thereby protecting ChREBP from degradation. SMURF2-mediated ChREBP degradation reduces aerobic glycolysis and cell proliferation in colorectal cancer cells. Co-immunoprecipitation; ubiquitination assay; SMURF2 overexpression and knockdown; AKT pharmacological inhibition; metabolic flux measurements The Journal of biological chemistry Medium 31409643
2013 Flightless I homolog (FLII), a gelsolin superfamily actin-remodeling protein, physically interacts with ChREBP and negatively regulates its transcriptional activity in cancer cells. The C-terminal 227 amino acids of ChREBP (containing the DNA-binding domain) interact with both LRR and GLD domains of FLII. FLII knockdown increases, and overexpression decreases, ChREBP target gene expression. Proteomic pulldown to identify interacting proteins; co-immunoprecipitation; co-localization by immunofluorescence; siRNA knockdown and overexpression of FLII The international journal of biochemistry & cell biology Medium 24055811
2011 ChREBP mediates glucose repression of PPARα gene expression in pancreatic β-cells: a constitutively active ChREBP efficiently represses PPARα expression, and siRNA knockdown of ChREBP abrogates glucose repression of PPARα as well as induction of established ChREBP target genes in insulinoma cells and rodent/human islets. Constitutively active ChREBP overexpression; siRNA knockdown of ChREBP; gene expression analysis in insulinoma cells and primary islets; PPARα promoter characterization The Journal of biological chemistry Medium 21282101
2015 ChREBP controls PPARγ activity in adipocytes in a fatty acid synthase (FASN)-dependent manner: constitutively active ChREBP activates endogenous PPARγ and promotes adipocyte differentiation by transactivating the PPARγ ligand-binding domain. Reducing ChREBP activity by siRNA, low glucose, or dominant-negative ChREBP impairs differentiation. Constitutively active ChREBP and dominant-negative ChREBP overexpression; siRNA knockdown; PPARγ ligand-binding domain reporter assay; adipocyte differentiation assay; FASN inhibitor treatment Endocrinology Medium 26181104
2018 ChREBP regulates hepatic VLDL secretion primarily through transcriptional activation of microsomal triglyceride transfer protein (MTTP); ChREBP overexpression induces Mttp mRNA and protein, while ChREBP KO markedly reduces VLDL particle number and secretion rates. SHP had negligible effect on Mttp expression under normal conditions and did not affect ChREBP transcriptional activity. Adenoviral overexpression of ChREBP and SHP in rat hepatocytes; promoter reporter assays; Shp-/-, Chrebp-/-, and Chrebp-/-Shp-/- mice; VLDL secretion rate measurements; mRNA/protein analysis Nutrients Medium 29518948
2016 mTORC2 (Rictor) in white adipose tissue controls ChREBP-β expression and de novo lipogenesis: adipocyte-specific deletion of Rictor decreases ChREBP-β expression, reduces adipose DNL, and impairs hepatic insulin sensitivity. mTORC2 promotes ChREBP-β expression in part by controlling glucose uptake. Adipocyte-specific Rictor knockout mice; ChREBP-β mRNA and lipogenic rate measurements; hepatic insulin sensitivity assays; high-fat diet metabolic phenotyping Nature communications Medium 27098609
2018 ChREBP and Myc cooperatively regulate hepatocyte proliferation and metabolism; ChREBP loss confers a proliferative disadvantage to normal murine hepatocytes (unlike Myc loss), and combined loss further impairs proliferation. ChREBP-controlled transcripts encode enzymes in glycolysis, TCA cycle, and β- and ω-FAO, while Myc-controlled transcripts encode glycolytic, glutaminolytic, and sterol biosynthetic enzymes. Both cooperatively upregulate ribosomal protein genes. Chrebp-/- and Myc-/- single and double KO mice; hepatoblastoma models; RNA-Seq; metabolic flux studies (oxidative phosphorylation, FAO, pyruvate dehydrogenase) The Journal of biological chemistry Medium 30087120
2024 ChREBP acts as an oncogene in hepatocellular carcinoma (HCC) by transcriptionally activating the PI3K regulatory subunit p85α to sustain PI3K/AKT signaling, while simultaneously rerouting glucose and glutamine metabolic fluxes into fatty acid and nucleic acid synthesis. Pharmacological inhibition of ChREBP by SBI-993 suppresses HCC tumor growth in vivo. ChREBP loss-of-function in HCC cells; ChREBP ChIP-Seq; metabolic flux analysis; p85α promoter assays; SBI-993 pharmacological inhibition in vivo xenograft model Nature communications High 38424041
2017 Retinol saturase (RetSat) functions upstream of ChREBP in liver: depletion of RetSat reduces ChREBP activity, lowering lipogenic gene expression and hepatic/circulating triglycerides. RetSat's effect on ChREBP is independent of its enzymatic product 13,14-dihydroretinol, suggesting a non-catalytic mechanism. Liver-specific RetSat depletion in dietary obese mice; ectopic ChREBP expression rescue; 13,14-dihydroretinol supplementation; hepatic TG and blood glucose measurement Nature communications Medium 28855500
2020 Liver ChREBP protects against fructose-induced glycogenic hepatotoxicity by transcriptionally activating L-type pyruvate kinase (LPK) to channel glucose-6-phosphate away from glycogen synthesis. Liver-specific ChREBP KO causes massive glycogen overload and decreased ATP in fructose-fed mice; hepatic LPK overexpression rescues these phenotypes. Liver-specific ChREBP KO mice; high-fructose diet; hepatic LPK adenoviral overexpression rescue; G6P measurements; ATP content assay; histology Diabetes High 31974143
2023 ChREBP transcriptionally activates hepatocyte growth factor activator (HGFAC) in mouse and human liver (identified via ChIP-Seq); HGFAC enhances lipid and glucose homeostasis partly through activation of hepatic PPARγ. HGFAC-KO mouse phenotypes are concordant with putative loss-of-function human HGFAC variants. ChREBP ChIP-Seq in mouse liver integrated with human GWAS data; HGFAC gain/loss-of-function mouse models; PPARγ activity assays JCI insight Medium 36413406
2021 Thyroid hormone receptor β1 (TRβ1) stimulates hepatic lipogenesis through ChREBP: hepatocyte-specific ChREBP KO abolishes TH-mediated induction of the lipogenic program and impairs regulation of fatty acid oxidation. TH regulates ChREBP activation and its recruitment to DNA. This pathway is conserved in human iPSC-derived hepatocytes. Hepatocyte-specific TRβ1 KO and ChREBP KO mice; T3 treatment; ChREBP ChIP; lipogenic gene expression; conservation in human iPSC-derived hepatocytes Science signaling Medium 34784250
2021 ChREBP, together with FoxO1, dually regulates TXNIP (thioredoxin-interacting protein) expression in hepatocytes: ChREBP is required for glucose/fed-state induction of TxNIP in liver, while FoxO1 is required for fasting-state induction. Both transcription factors are identified by ChIP and loss-of-function studies in genetically modified mice. ChREBP KO and FoxO1 KO mice; ChIP-qPCR; reporter assays; nutritional state manipulation iScience Medium 33748706
2022 Hepatocyte KCTD17 promotes ChREBP protein stabilization by inducing degradation of O-GlcNAcase (OGA), thereby increasing O-GlcNAcylated ChREBP levels. SREBP1c induces KCTD17 expression in obesity. Hepatocyte-specific KCTD17 KO in HFD-fed mice improves glucose tolerance and hepatic steatosis; this is reversed by concomitant OGA KO. CRISPR-Cas9 hepatocyte-specific KO (Kctd17, Oga, double KO); AAV delivery; OGA protein stability assay; ChREBP protein level and target gene analysis; HFD metabolic phenotyping Gastroenterology High 36402191
2022 Celastrol directly binds to ChREBP (confirmed by molecular docking, CETSA, DARTS, and mass spectrometry), inhibits ChREBP nuclear translocation, and promotes its proteasomal degradation, thereby repressing TXNIP transcription and ameliorating type 2 diabetes in db/db mice. Molecular docking; cellular thermal shift assay (CETSA); drug affinity responsive target stability (DARTS); mass spectrometry; nuclear fractionation; gain/loss-of-function (ChREBP and TXNIP); db/db mouse model Phytomedicine Medium 36603341
2023 ChREBP induces mitochondrial fragmentation in kidney podocytes through upregulation of ether phospholipid biosynthesis: ChREBP transcriptionally activates Gnpat (glyceronephosphate O-acyltransferase), a critical enzyme in plasmalogen synthesis, and overexpression of GNPAT reverses the protective effect of ChREBP deficiency on mitochondrial fragmentation. Inducible podocyte-specific ChREBP KD in db/db mice; lipidomics; GNPAT overexpression rescue; ChREBP ChIP; electron microscopy for mitochondrial morphology The Journal of biological chemistry Medium 37611830
2018 ChREBP and its heterodimer partner Mlx cooperate to activate the Glut5 promoter in intestinal cells; ChIP assay demonstrates direct binding of ChREBP to the Glut5 ChoRE in small intestine, but not to the NHE3 promoter. ChIP assay in mouse small intestine; co-transfection promoter reporter assay in Caco-2BBE cells with ChREBP + Mlx Metabolism: clinical and experimental Medium 29669261
2018 ChREBP directly regulates de novo lipogenesis in interplay with SREBP-1c: both transcription factors are required for coordinated postprandial induction of glycolytic and lipogenic mRNAs. ChREBP mediates glucose induction of both glycolytic and lipogenic genes, while SREBP-1c mediates insulin induction of lipogenic genes. ChREBP is also required for normal SREBP-1c mRNA and protein levels in the fed state. Liver-specific ChREBP KO mice; AAV-mediated nuclear SREBP-1c restoration; Scap-deficient mice (lack active SREBPs); sucrose refeeding paradigm; mRNA and protein measurements Journal of lipid research High 29335275
2014 High glucose activates nuclear translocation of ChREBP in retinal pigment epithelial (RPE) cells under normoxia, and ChREBP associates with the HIF-1α gene promoter, driving HIF-1α and VEGF expression. This phenomenon is cell-type specific (not observed in lens epithelial or HeLa cells). Immunofluorescence for ChREBP nuclear localization; ChIP for ChREBP at HIF-1α promoter; ELISA for VEGF; RT-PCR; immunoblot Advances in experimental medicine and biology Low 24664750

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism. Nature 495 22466288
2006 Carbohydrate response element binding protein, ChREBP, a transcription factor coupling hepatic glucose utilization and lipid synthesis. Cell metabolism 417 16890538
2008 Genome-wide scan identifies variation in MLXIPL associated with plasma triglycerides. Nature genetics 260 18193046
2013 De novo lipogenesis in human fat and liver is linked to ChREBP-β and metabolic health. Nature communications 256 23443556
2005 Carbohydrate responsive element binding protein (ChREBP) and sterol regulatory element binding protein-1c (SREBP-1c): two key regulators of glucose metabolism and lipid synthesis in liver. Biochimie 256 15733741
2013 Transcriptional control of hepatic lipid metabolism by SREBP and ChREBP. Seminars in liver disease 234 24222088
2005 Polyunsaturated fatty acids suppress glycolytic and lipogenic genes through the inhibition of ChREBP nuclear protein translocation. The Journal of clinical investigation 230 16184193
2007 ChREBP, a transcriptional regulator of glucose and lipid metabolism. Annual review of nutrition 210 17428181
2018 Interplay between ChREBP and SREBP-1c coordinates postprandial glycolysis and lipogenesis in livers of mice. Journal of lipid research 190 29335275
2017 Sweet Sixteenth for ChREBP: Established Roles and Future Goals. Cell metabolism 180 28768172
2016 ChREBP regulates fructose-induced glucose production independently of insulin signaling. The Journal of clinical investigation 176 27669460
2011 O-GlcNAcylation increases ChREBP protein content and transcriptional activity in the liver. Diabetes 173 21471514
2008 ChREBP: a glucose-activated transcription factor involved in the development of metabolic syndrome. Endocrine journal 173 18490833
2013 Novel insights into ChREBP regulation and function. Trends in endocrinology and metabolism: TEM 165 23597489
2008 ChREBP, but not LXRs, is required for the induction of glucose-regulated genes in mouse liver. The Journal of clinical investigation 163 18292813
2002 Carbohydrate responsive element-binding protein (ChREBP): a key regulator of glucose metabolism and fat storage. Biochemical pharmacology 155 12110366
2016 Adipose tissue mTORC2 regulates ChREBP-driven de novo lipogenesis and hepatic glucose metabolism. Nature communications 149 27098609
2016 A critical role for ChREBP-mediated FGF21 secretion in hepatic fructose metabolism. Molecular metabolism 142 28123933
2011 CREB and ChREBP oppositely regulate SIRT1 expression in response to energy availability. EMBO reports 140 21836635
2019 Carbohydrate Sensing Through the Transcription Factor ChREBP. Frontiers in genetics 132 31275349
2009 The glucose-responsive transcription factor ChREBP contributes to glucose-dependent anabolic synthesis and cell proliferation. Proceedings of the National Academy of Sciences of the United States of America 119 19995986
2007 Role of ChREBP in hepatic steatosis and insulin resistance. FEBS letters 115 17716660
2017 A Specific ChREBP and PPARα Cross-Talk Is Required for the Glucose-Mediated FGF21 Response. Cell reports 107 29020627
2020 ChREBP-Mediated Regulation of Lipid Metabolism: Involvement of the Gut Microbiota, Liver, and Adipose Tissue. Frontiers in endocrinology 105 33343508
2012 ChREBP mediates glucose-stimulated pancreatic β-cell proliferation. Diabetes 102 22586588
2001 WBSCR14, a gene mapping to the Williams--Beuren syndrome deleted region, is a new member of the Mlx transcription factor network. Human molecular genetics 93 11230181
2008 Regulation of nuclear import/export of carbohydrate response element-binding protein (ChREBP): interaction of an alpha-helix of ChREBP with the 14-3-3 proteins and regulation by phosphorylation. The Journal of biological chemistry 92 18606808
2013 Mondo/ChREBP-Mlx-regulated transcriptional network is essential for dietary sugar tolerance in Drosophila. PLoS genetics 91 23593032
2002 ChREBP rather than USF2 regulates glucose stimulation of endogenous L-pyruvate kinase expression in insulin-secreting cells. The Journal of biological chemistry 91 12087089
2019 Long non-coding RNA (lncRNA) H19 induces hepatic steatosis through activating MLXIPL and mTORC1 networks in hepatocytes. Journal of cellular and molecular medicine 83 31809000
2017 Intestinal, but not hepatic, ChREBP is required for fructose tolerance. JCI insight 79 29263303
2009 Replacing dietary glucose with fructose increases ChREBP activity and SREBP-1 protein in rat liver nucleus. Biochemical and biophysical research communications 79 19799862
2012 Carbohydrate response element-binding protein (ChREBP) plays a pivotal role in beta cell glucotoxicity. Diabetologia 75 22382520
2014 ChREBP, a glucose-responsive transcriptional factor, enhances glucose metabolism to support biosynthesis in human cytomegalovirus-infected cells. Proceedings of the National Academy of Sciences of the United States of America 73 24449882
2023 The role of ChREBP in carbohydrate sensing and NAFLD development. Nature reviews. Endocrinology 70 37055547
2006 Hepatic gene regulation by glucose and polyunsaturated fatty acids: a role for ChREBP. The Journal of nutrition 68 16614395
2011 Cross-regulation of hepatic glucose metabolism via ChREBP and nuclear receptors. Biochimica et biophysica acta 66 21453770
2017 mTOR controls ChREBP transcriptional activity and pancreatic β cell survival under diabetic stress. The Journal of cell biology 60 28606928
2000 WBSCR14, a putative transcription factor gene deleted in Williams-Beuren syndrome: complete characterisation of the human gene and the mouse ortholog. European journal of human genetics : EJHG 60 10780788
2016 The transcription factor carbohydrate-response element-binding protein (ChREBP): A possible link between metabolic disease and cancer. Biochimica et biophysica acta. Molecular basis of disease 59 27919710
2023 Aberrant elevation of FTO levels promotes liver steatosis by decreasing the m6A methylation and increasing the stability of SREBF1 and ChREBP mRNAs. Journal of molecular cell biology 57 36352530
2011 ChREBP expression in the liver, adipose tissue and differentiated preadipocytes in human obesity. Biochimica et biophysica acta 56 21840420
2015 The Glucose Sensor ChREBP Links De Novo Lipogenesis to PPARγ Activity and Adipocyte Differentiation. Endocrinology 55 26181104
2013 Recent progress on the role of ChREBP in glucose and lipid metabolism. Endocrine journal 53 23604004
2021 Adaptive and maladaptive roles for ChREBP in the liver and pancreatic islets. The Journal of biological chemistry 51 33812993
2008 Regulation of lipogenesis via BHLHB2/DEC1 and ChREBP feedback looping. Biochemical and biophysical research communications 50 18602890
2024 The transcription factor ChREBP Orchestrates liver carcinogenesis by coordinating the PI3K/AKT signaling and cancer metabolism. Nature communications 49 38424041
2010 c-Myc is required for the CHREBP-dependent activation of glucose-responsive genes. Molecular endocrinology (Baltimore, Md.) 47 20382893
2019 HCF-1 Regulates De Novo Lipogenesis through a Nutrient-Sensitive Complex with ChREBP. Molecular cell 46 31227231
2018 Interaction between hormone-sensitive lipase and ChREBP in fat cells controls insulin sensitivity. Nature metabolism 46 32694809
2017 MondoA/ChREBP: The usual suspects of transcriptional glucose sensing; Implication in pathophysiology. Metabolism: clinical and experimental 44 28403938
2018 ChREBP deficiency leads to diarrhea-predominant irritable bowel syndrome. Metabolism: clinical and experimental 42 29669261
2015 FABP4-Cre Mediated Expression of Constitutively Active ChREBP Protects Against Obesity, Fatty Liver, and Insulin Resistance. Endocrinology 42 26248218
2016 ChREBP Regulates Itself and Metabolic Genes Implicated in Lipid Accumulation in β-Cell Line. PloS one 41 26808438
2015 Integration of ChREBP-Mediated Glucose Sensing into Whole Body Metabolism. Physiology (Bethesda, Md.) 41 26525342
2021 SIRT6 controls hepatic lipogenesis by suppressing LXR, ChREBP, and SREBP1. Biochimica et biophysica acta. Molecular basis of disease 40 34425214
2020 Reduced Nogo expression inhibits diet-induced metabolic disorders by regulating ChREBP and insulin activity. Journal of hepatology 40 32738448
2011 Isoflavones as a smart curer for non-alcoholic fatty liver disease and pathological adiposity via ChREBP and Wnt signaling. Preventive medicine 40 22227283
2019 The ubiquitination ligase SMURF2 reduces aerobic glycolysis and colorectal cancer cell proliferation by promoting ChREBP ubiquitination and degradation. The Journal of biological chemistry 39 31409643
2018 Recent insights into the role of ChREBP in intestinal fructose absorption and metabolism. BMB reports 38 30158026
2017 Retinol saturase coordinates liver metabolism by regulating ChREBP activity. Nature communications 37 28855500
2011 ChREBP mediates glucose repression of peroxisome proliferator-activated receptor alpha expression in pancreatic beta-cells. The Journal of biological chemistry 37 21282101
2020 Liver ChREBP Protects Against Fructose-Induced Glycogenic Hepatotoxicity by Regulating L-Type Pyruvate Kinase. Diabetes 36 31974143
2018 ChREBP-Knockout Mice Show Sucrose Intolerance and Fructose Malabsorption. Nutrients 36 29534502
2018 Myc and ChREBP transcription factors cooperatively regulate normal and neoplastic hepatocyte proliferation in mice. The Journal of biological chemistry 34 30087120
2012 Structural characterization of a unique interface between carbohydrate response element-binding protein (ChREBP) and 14-3-3β protein. The Journal of biological chemistry 34 23086940
2021 Thyroid hormone signaling promotes hepatic lipogenesis through the transcription factor ChREBP. Science signaling 33 34784250
2018 ChREBP Reciprocally Regulates Liver and Plasma Triacylglycerol Levels in Different Manners. Nutrients 33 30405056
2011 Importin-alpha protein binding to a nuclear localization signal of carbohydrate response element-binding protein (ChREBP). The Journal of biological chemistry 33 21665952
2021 Single-cell analysis reveals the intra-tumor heterogeneity and identifies MLXIPL as a biomarker in the cellular trajectory of hepatocellular carcinoma. Cell death discovery 31 33462196
2019 Quercetin inhibition of SREBPs and ChREBP expression results in reduced cholesterol and fatty acid synthesis in C6 glioma cells. The international journal of biochemistry & cell biology 31 31542428
2015 O-GlcNAcylation Links ChREBP and FXR to Glucose-Sensing. Frontiers in endocrinology 31 25628602
2014 High glucose activates ChREBP-mediated HIF-1α and VEGF expression in human RPE cells under normoxia. Advances in experimental medicine and biology 31 24664750
2023 Recent Progress on Fructose Metabolism-Chrebp, Fructolysis, and Polyol Pathway. Nutrients 30 37049617
2023 Acetyl-CoA synthetase 2 promotes diabetic renal tubular injury in mice by rewiring fatty acid metabolism through SIRT1/ChREBP pathway. Acta pharmacologica Sinica 30 37770579
2020 Carbohydrate response element binding protein (ChREBP) correlates with colon cancer progression and contributes to cell proliferation. Scientific reports 30 32144313
2020 ChREBP-β regulates thermogenesis in brown adipose tissue. The Journal of endocrinology 27 32208359
2018 Carvacrol reduces adipogenic differentiation by modulating autophagy and ChREBP expression. PloS one 27 30418986
2017 Sugar-sweetened beverage intake associations with fasting glucose and insulin concentrations are not modified by selected genetic variants in a ChREBP-FGF21 pathway: a meta-analysis. Diabetologia 27 29098321
2022 ChREBP-driven DNL and PNPLA3 Expression Induced by Liquid Fructose are Essential in the Production of Fatty Liver and Hypertriglyceridemia in a High-Fat Diet-Fed Rat Model. Molecular nutrition & food research 26 35124887
2017 Validation, Identification, and Biological Consequences of the Site-specific O-GlcNAcylation Dynamics of Carbohydrate-responsive Element-binding Protein (ChREBP). Molecular & cellular proteomics : MCP 25 28450420
2015 ChREBP binding and histone modifications modulate hepatic expression of the Fasn gene in a metabolic syndrome rat model. Nutrition (Burbank, Los Angeles County, Calif.) 25 25933497
2018 T3 and Glucose Coordinately Stimulate ChREBP-Mediated Ucp1 Expression in Brown Adipocytes From Male Mice. Endocrinology 24 29077876
2024 Acute hyperglycemia exacerbates neuroinflammation and cognitive impairment in sepsis-associated encephalopathy by mediating the ChREBP/HIF-1α pathway. European journal of medical research 23 39538358
2023 HGFAC is a ChREBP-regulated hepatokine that enhances glucose and lipid homeostasis. JCI insight 23 36413406
2020 TXNIP induced by MondoA, rather than ChREBP, suppresses cervical cancer cell proliferation, migration and invasion. Journal of biochemistry 23 31782782
2018 ChREBP Rather Than SHP Regulates Hepatic VLDL Secretion. Nutrients 23 29518948
2022 Inhibition of ChREBP ubiquitination via the ROS/Akt-dependent downregulation of Smurf2 contributes to lysophosphatidic acid-induced fibrosis in renal mesangial cells. Journal of biomedical science 22 35538534
2020 Dietary Glucose Increases Glucose Absorption and Lipid Deposition via SGLT1/2 Signaling and Acetylated ChREBP in the Intestine and Isolated Intestinal Epithelial Cells of Yellow Catfish. The Journal of nutrition 22 32470978
2023 ChREBP-β/TXNIP aggravates frucose-induced renal injury through triggering ferroptosis of renal tubular epithelial cells. Free radical biology & medicine 20 36828294
2022 Celastrol targets the ChREBP-TXNIP axis to ameliorates type 2 diabetes mellitus. Phytomedicine : international journal of phytotherapy and phytopharmacology 20 36603341
2021 Dual regulation of TxNIP by ChREBP and FoxO1 in liver. iScience 20 33748706
2013 Flightless I homolog negatively regulates ChREBP activity in cancer cells. The international journal of biochemistry & cell biology 20 24055811
2020 Role for carbohydrate response element-binding protein (ChREBP) in high glucose-mediated repression of long noncoding RNA Tug1. The Journal of biological chemistry 19 32467232
2019 Glucose-Sensing Transcription Factor MondoA/ChREBP as Targets for Type 2 Diabetes: Opportunities and Challenges. International journal of molecular sciences 19 31623194
2017 Advanced glycation end products promote ChREBP expression and cell proliferation in liver cancer cells by increasing reactive oxygen species. Medicine 19 28816938
2023 The transcription factor ChREBP links mitochondrial lipidomes to mitochondrial morphology and progression of diabetic kidney disease. The Journal of biological chemistry 18 37611830
2022 Hepatocyte Kctd17 Inhibition Ameliorates Glucose Intolerance and Hepatic Steatosis Caused by Obesity-induced Chrebp Stabilization. Gastroenterology 18 36402191
2011 ChREBP gene polymorphisms are associated with coronary artery disease in Han population of Hubei province. Clinica chimica acta; international journal of clinical chemistry 18 21726544
2021 ChREBP deficiency alleviates apoptosis by inhibiting TXNIP/oxidative stress in diabetic nephropathy. Journal of diabetes and its complications 17 34600826

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