Affinage

FBP1

Fructose-1,6-bisphosphatase 1 · UniProt P09467

Length
338 aa
Mass
36.8 kDa
Annotated
2026-06-09
100 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FBP1 is a gluconeogenic enzyme that catalyzes hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate and inorganic phosphate (PMID:7558035), and which functions broadly as a metabolic brake on glycolysis whose loss reprograms cells toward the Warburg effect across diverse tissues (PMID:23453623, PMID:3003364). In the liver, hepatic FBP1 is required for fructose tolerance—its deletion drives fructose-1-phosphate accumulation, steatosis, and injury (PMID:36964915)—and its loss promotes tumorigenesis through HMGB1 release that activates and senesces hepatic stellate cells (PMID:32367049), while in the MASH-to-HCC transition FBP1 acts as a p53-regulated enforcer of senescence whose degradation enables progression (PMID:39743585). Beyond catalysis, FBP1 restrains glycolysis by suppressing HIF-1α and occupying hypoxia response elements at glycolytic gene promoters (PMID:28485159), and it executes several non-enzymatic tumor-suppressor functions: physically engaging STAT3 to block its nuclear translocation (PMID:34363022), binding the BRD4 BD2 bromodomain in a Tip60-acetylation-dependent manner to downregulate BRD4 target genes (PMID:32195024), scaffolding NICD1–FBXW7 to drive Notch1 degradation independently of its enzymatic activity (PMID:38349431), and translocating to the nucleus to interact with DNMT1 and trap PARP1 on chromatin (PMID:34854226). FBP1 levels are controlled by an extensive regulatory network: transcriptional repression via the Snail–G9a–DNMT1 complex (PMID:23453623), HDAC1/2-mediated H3K27Ac loss (PMID:28262837), and repressors C-MYC, FOXC1, Ets1, and KDM5A (PMID:30171256, PMID:34363022, PMID:31444412, PMID:37713600), opposed by activators C/EBPα, HNF4α, retinoic-acid receptor, and FOXP2 (PMID:29566023, PMID:35672803, PMID:37713600); and post-translationally by ubiquitin ligases MAGE-TRIM28, TRIM47, SKP2 (downstream of PTEN/AKT/CDK-driven S271 phosphorylation), and UBR5 versus the stabilizing deubiquitinases USP44 and USP7 (PMID:28394358, PMID:33529753, PMID:36237339, PMID:33122826, PMID:31497353, PMID:34854226). Context-dependently, FBP1 is co-opted as a pro-tumor effector in Evi1-driven leukemia, where it feeds the pentose phosphate pathway (PMID:34363719), and impairs NK-cell antitumor function by inhibiting glycolysis (PMID:30033198).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1985 High

    Established the molecular identity of the FBP1 gene product as fructose bisphosphatase and revealed glucose-repressible expression, defining the core gluconeogenic function.

    Evidence Gene cloning by complementation, transplacement disruption, and heterologous enzymatic assay in S. cerevisiae

    PMID:3003364

    Open questions at the time
    • Yeast ortholog; human gene structure not yet defined
    • Regulatory transcription factors not identified
  2. 1991 High

    Mapped the upstream signaling that controls fbp1 transcription, showing glucose repression operates through the cAMP-PKA pathway.

    Evidence Genetic epistasis with git mutants, fbp1-reporter fusions, and cAMP rescue in S. pombe

    PMID:1849107

    Open questions at the time
    • Downstream transcription factors at the promoter not yet defined
    • Yeast pathway; mammalian relevance unestablished
  3. 1995 High

    Defined the human FBP1 gene structure, enzymatic reaction, and chromosomal locus, anchoring the canonical metabolic function in humans.

    Evidence Gene cloning, exon-intron mapping, and FISH localization to 9q22

    PMID:7558035

    Open questions at the time
    • No regulatory or non-enzymatic functions addressed
    • Disease relevance not yet established
  4. 2000 High

    Dissected the promoter logic of fbp1, showing antagonistic PKA/MAPK control through distinct upstream activation sites and the atf1-pcr1 activator complex.

    Evidence Promoter deletion, EMSA, and signaling-mutant reporter analysis in S. pombe

    PMID:10938120 PMID:11238405 PMID:14573465 PMID:8001792

    Open questions at the time
    • Yeast transcriptional architecture may not map onto mammalian FBP1 regulation
    • Chromatin-level mechanism elaborated only in fission yeast
  5. 2011 High

    Revealed a non-degradative ubiquitination role, where USP22 deubiquitinates FBP1 to control its occupancy at the p21 promoter and thus proliferation.

    Evidence USP22 knockdown, ubiquitination assays, and ChIP at the p21 locus

    PMID:21779003

    Open questions at the time
    • This FBP1 (FUSE-binding protein context) chromatin role not connected to metabolic FBP1 function
    • Mechanism of promoter occupancy unresolved
  6. 2013 High

    Established FBP1 as a metabolic tumor suppressor whose epigenetic silencing reprograms cells toward glycolysis and stemness, motivating the broad oncology framework.

    Evidence Promoter methylation/ChIP, metabolic flux assays, and β-catenin co-IP in basal-like breast cancer

    PMID:23453623

    Open questions at the time
    • Whether tumor suppression requires enzymatic activity not separated here
    • Generality across tumor types not yet tested
  7. 2017 High

    Identified the first ubiquitin ligase axis and an enhancer-level epigenetic repressor controlling FBP1 protein and transcript levels in HCC.

    Evidence Co-IP, in vivo ubiquitination, and H3K27Ac ChIP with HDAC inhibition (MAGE-TRIM28; HDAC1/2)

    PMID:28262837 PMID:28394358

    Open questions at the time
    • Degron/recognition motif on FBP1 not mapped
    • Crosstalk between transcriptional and post-translational control unaddressed
  8. 2018 High

    Broadened FBP1 biology beyond tumor cells (impairing NK antitumor function) and detailed its transcriptional activators and HIF-1α suppression.

    Evidence NK cell manipulation with glycolysis assays; promoter mutagenesis/EMSA (C/EBPα, HNF4α); FBP1 overexpression with HRE ChIP

    PMID:28485159 PMID:29566023 PMID:30033198 PMID:30171256

    Open questions at the time
    • Mechanism of FBP1 occupancy at HREs unclear
    • Whether NK-intrinsic effect is enzymatic unresolved
  9. 2020 High

    Defined the non-cell-autonomous liver tumor-suppressor mechanism (HMGB1-driven stellate cell activation) and expanded the regulatory network of ligases, deubiquitinases, RNA-binding stabilizers, and non-enzymatic protein interactions.

    Evidence Conditional KO mice with HMGB1 inhibition; co-IP/ubiquitination (UBR5-C/EBPα); RIP (CELF6); FBP1-BRD4 domain mapping; FBP1-STAT3 co-IP; LOXL2/HSF2/GATA4 functional studies

    PMID:31497345 PMID:31497353 PMID:31892855 PMID:32195024 PMID:32323822 PMID:32367049 PMID:32601971 PMID:33122826

    Open questions at the time
    • Non-enzymatic interactions largely from single labs without reciprocal validation
    • Structural basis of FBP1-BRD4 and FBP1-STAT3 binding unresolved
  10. 2021 Medium

    Established phosphorylation-coupled degradation (PTEN/AKT/CDK-S271/SKP2) and a nuclear FBP1-DNMT1-PARP1 axis, and revealed context-dependent pro-tumor co-option in Evi1 leukemia.

    Evidence S271 phospho-mutagenesis with ubiquitination assays; USP7/FBP1/DNMT1 co-IPs with chromatin PARP1 assays; Evi1 enhancer ChIP with metabolomics

    PMID:33529753 PMID:34298040 PMID:34363022 PMID:34363719 PMID:34854226 PMID:36237339

    Open questions at the time
    • S271 kinase identity not pinned to a specific CDK
    • Pro- vs anti-tumor switch determinants not defined
  11. 2024 Medium

    Resolved enzymatic-independent Notch suppression and connected FBP1 loss to glycolysis-driven histone acetylation in non-cancer disease (psoriasis), plus FBXW7 stabilization controlling mTOR.

    Evidence FBP1-NICD1-FBXW7 complex co-IP with enzyme-dead mutant; acetyl-CoA/H3K9Ac ChIP in keratinocytes; FBXW7-mTOR ubiquitination assays

    PMID:34298040 PMID:38238754 PMID:38349431 PMID:38834617

    Open questions at the time
    • Enzymatic vs scaffold contributions not fully separated across contexts
    • Single-lab validation for most interaction claims
  12. 2025 High

    Positioned FBP1 within a p53-dependent senescence program that gatekeeps MASH-to-HCC progression, integrating transcriptional and degradative control.

    Evidence p53 ChIP, AKT/NRF2 gain/loss, proteasomal degradation and methylation assays in mouse MASH-HCC models

    PMID:39743585

    Open questions at the time
    • Whether senescence enforcement requires FBP1 enzymatic activity not resolved
    • Direct molecular link between FBP1 and p53 stability not fully mechanistic

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved which FBP1 functions require its catalytic activity versus non-enzymatic scaffolding, and how the dense regulatory network is integrated to set FBP1 levels in a given tissue or tumor context.
  • No unified structural model distinguishing enzymatic and protein-interaction surfaces
  • Determinants of pro-tumor vs tumor-suppressor behavior undefined
  • Reciprocal/independent validation lacking for many single-lab interaction claims

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005694 chromosome 3 GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-1643685 Disease 3 R-HSA-392499 Metabolism of proteins 3
Partners
BRD4DNMT1FBXW7GATA4SKP2STAT3TRIM28USP7

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 The Snail-G9a-Dnmt1 complex mediates promoter methylation and transcriptional repression of FBP1 in basal-like breast cancer. Loss of FBP1 induces glycolysis, increases glucose uptake, promotes tetrameric PKM2 formation, maintains ATP production under hypoxia, suppresses mitochondrial complex I activity and ROS production, and enhances β-catenin/TCF interaction to confer cancer stem cell-like properties. Promoter methylation analysis, ChIP, metabolic assays (glucose uptake, ATP, ROS, oxygen consumption), co-immunoprecipitation of β-catenin/TCF, loss-of-function and gain-of-function experiments in BLBC cells Cancer cell High 23453623
2018 Aberrant FBP1 expression in NK cells inhibits glycolysis and impairs NK cell viability and antitumor function during lung cancer progression. FBP1 manipulation in primary NK cells, glycolysis assays (glucose uptake, lactate production, ECAR), functional cytotoxicity assays, in vivo Kras-driven lung cancer model Cell metabolism High 30033198
2020 Hepatocyte-specific loss of FBP1 causes liver steatosis and promotes hepatic stellate cell (HSC) activation and senescence via HMGB1 release from FBP1-deficient hepatocytes. Blocking HMGB1 with inflachromene limits FBP1-dependent HSC activation and the subsequent senescence-associated secretory phenotype (SASP), establishing FBP1 as a metabolic tumor suppressor in liver cancer. Hepatocyte-specific Fbp1 conditional knockout mice, senolytic drug treatment (dasatinib/quercetin, ABT-263), HMGB1 inhibition with inflachromene, co-culture experiments, tumor progression assays Nature cell biology High 32367049
2017 MAGE-A3/C2-TRIM28 ubiquitin ligase complexes bind directly to FBP1 and promote its ubiquitination and proteasomal degradation, thereby enhancing the Warburg effect and hepatocellular carcinoma growth. Co-immunoprecipitation (direct binding of TRIM28 to FBP1), in vivo ubiquitination assays, glucose consumption/lactate production assays, xenograft mouse models, bortezomib proteasome inhibition rescue Oncogenesis High 28394358
2011 USP22 deubiquitinates FBP1 (FUSE-binding protein 1); loss of USP22 increases FBP1 polyubiquitination without affecting its protein stability, but instead reduces FBP1 occupancy at the p21 gene promoter, thereby decreasing p21 expression and promoting cell proliferation. USP22 knockdown, ubiquitination assays, chromatin immunoprecipitation (ChIP) for FBP1 at p21 locus, p21 expression analysis EMBO reports High 21779003
2020 E3 ubiquitin ligase UBR5 promotes FBP1 downregulation by directly binding to and ubiquitinating/degrading the transcription factor C/EBPα, which is required for FBP1 transcription, thereby activating aerobic glycolysis and pancreatic cancer growth. Co-immunoprecipitation (UBR5 binding to C/EBPα), ubiquitination assays, UBR5 knockdown/overexpression, FBP1 rescue experiments, in vivo xenograft models Oncogene High 33122826
2021 TRIM47 directly binds to and ubiquitinates FBP1, promoting its degradation and thereby accelerating aerobic glycolysis and pancreatic cancer progression. Co-immunoprecipitation (TRIM47 direct binding to FBP1), ubiquitination assays, TRIM47 knockdown/overexpression, FBP1 overexpression rescue, in vivo xenograft assays Pharmacological research Medium 33529753
2019 USP44 binds to FBP1 and promotes its deubiquitination, stabilizing FBP1 protein levels and suppressing pancreatic cancer progression and gemcitabine resistance. Co-immunoprecipitation, deubiquitination assays, USP44 knockdown/overexpression, FBP1 protein stability analysis American journal of cancer research Medium 31497353
2021 USP7 binds to and deubiquitinates FBP1, preventing its translocation to the nucleus. Nuclear FBP1 interacts with DNMT1 and traps PARP1 on chromatin, sensitizing pancreatic cancer cells to PARP inhibitors. USP7 inhibitors enhance PARP inhibitor antitumor effects in an FBP1-dependent manner. Co-immunoprecipitation (USP7-FBP1 and FBP1-DNMT1 interactions), deubiquitination assays, nuclear fractionation, chromatin-bound PARP1 assays, USP7 inhibitor functional assays Molecular oncology Medium 34854226
2022 PTEN loss activates PI3K/AKT signaling, which promotes CDK-mediated phosphorylation of FBP1 at serine 271, enabling SKP2 E3 ubiquitin ligase-mediated ubiquitination and proteasomal degradation of FBP1, thus enhancing the Warburg effect and prostate cancer growth. Co-immunoprecipitation (SKP2-FBP1), in vivo ubiquitination assays, phospho-site mutagenesis (S271), PTEN-null cell lines and xenograft models Frontiers in oncology Medium 36237339
2017 HDAC1/HDAC2 repress FBP1 expression in hepatocellular carcinoma by reducing histone H3 lysine 27 acetylation (H3K27Ac) at the FBP1 enhancer. HDAC inhibitor treatment or HDAC1/2 knockdown restores FBP1 expression and suppresses HCC cell growth. ChIP for H3K27Ac at FBP1 enhancer, HDAC1/2 knockdown and inhibitor treatment, FBP1 expression and glycolysis assays, in vitro and in vivo tumor growth assays Scientific reports Medium 28262837
2018 FOXC1 binds directly to the FBP1 gene promoter and negatively regulates its transcriptional activity, thereby promoting glycolysis and colorectal cancer proliferation. ChIP assay (FOXC1 binding to FBP1 promoter), luciferase reporter assay, FOXC1 knockdown/overexpression, glycolysis assays, xenograft models Oncogene Medium 30171256
2020 FBP1 physically interacts with BRD4, binding to its BD2 bromodomain in an acetylation-dependent manner. Tip60 acetylates FBP1 at K110 and K113, and HDAC3 removes these marks; this acetylation is critical for FBP1-BRD4 binding in pancreatic cancer cells. FBP1-BRD4 interaction decreases expression of BRD4 target genes to inhibit pancreatic cancer progression. Co-immunoprecipitation (FBP1-BRD4), domain mapping (BD2), acetylation-site mutagenesis (K110/K113), Tip60 and HDAC3 functional assays, downstream gene expression analysis American journal of cancer research Medium 32195024
2024 FBP1 interacts with NICD1 (Notch1 intracellular domain) and the E3 ubiquitin ligase FBXW7 to facilitate ubiquitin-proteasome-dependent degradation of NICD1, inhibiting Notch signaling and NSCLC stemness. This function is independent of FBP1's metabolic enzymatic activity. Co-immunoprecipitation (FBP1-NICD1-FBXW7 complex), ubiquitination assays, enzymatic activity mutant of FBP1, CD133+ stem cell proportion analysis, tumorigenicity assays Cellular and molecular life sciences Medium 38349431
2021 FBP1 physically interacts with STAT3 and suppresses nuclear translocation of STAT3, exerting non-enzymatic activity to impair STAT3 function in ovarian cancer cells. C-MYC binding to the FBP1 promoter inhibits FBP1 transcription (alongside DNA methylation). Co-immunoprecipitation (FBP1-STAT3), nuclear fractionation, ChIP (C-MYC at FBP1 promoter), FBP1 overexpression functional assays Oncogene Medium 34363022
2024 FBP1 promotes FBP1 radiosensitivity in nasopharyngeal carcinoma by stabilizing FBXW7 protein (through suppressing FBXW7 auto-ubiquitination), which in turn promotes ubiquitination and degradation of mTOR, thereby suppressing glycolysis. Co-immunoprecipitation (FBXW7-FBP1 and FBXW7-mTOR), ubiquitination assays, FBP1 gain/loss-of-function, glycolysis assays, xenograft models Life sciences Medium 34298040
2019 Ets1 transcription factor is overexpressed in irradiation-induced glioblastoma and acts as a transcriptional repressor of FBP1, leading to decreased FBP1 expression, elevated glycolysis, and increased GBM invasiveness after radiation. FBP1 expression analysis post-irradiation, Ets1 ChIP/promoter analysis, glycolysis assays (glucose uptake, ECAR), orthotopic xenograft mouse model Oncogene Medium 31444412
2018 C/EBPα binds to two overlapping sites at nucleotide -228/-208 of the FBP1 promoter, and HNF4α binds to H4-SBM and DR3 sites at -566/-554 and -212/-198, respectively, to activate FBP1 transcription in hepatoma HepG2 cells. Mutation of these sites markedly reduces transcriptional activation. Luciferase reporter assays with promoter mutations, electrophoretic mobility shift assay (EMSA), siRNA knockdown of C/EBPα and HNF4α PloS one Medium 29566023
2024 FBP1 loss in keratinocytes facilitates glycolysis-mediated acetyl-CoA production, which increases histone H3 lysine 9 acetylation (H3K9Ac), leading to enhanced transcription of proliferation genes. This mechanism promotes keratinocyte proliferation while inhibiting differentiation and exacerbates psoriasis-like phenotypes. Fbp1 heterozygous mice (epidermis phenotyping), in vitro keratinocyte FBP1 loss-of-function, acetyl-CoA measurement, H3K9Ac ChIP, transcriptome sequencing, imiquimod psoriasis mouse model Cell death & disease Medium 38834617
2025 FBP1 is a p53 transcriptional target elevated in senescent MASH hepatocytes. FBP1 is suppressed in HCC progenitor cells through promoter hypermethylation and proteasomal degradation driven by AKT and NRF2 activation. AKT and NRF2 accelerate both FBP1 and p53 degradation, reversing senescence and enabling proliferation and metabolic reprogramming needed for MASH-to-HCC progression. p53 ChIP (FBP1 as p53 target), AKT/NRF2 gain/loss-of-function, proteasomal degradation assays, promoter methylation analysis, mouse MASH-HCC models Nature High 39743585
2023 Hepatic but not intestinal FBP1 is required for fructose metabolism and tolerance. Liver-specific Fbp1 deletion in mice leads to fructose-1-phosphate accumulation (indicative of defective fructolysis, likely due to competitive inhibition by fructose-1,6-bisphosphate), hepatomegaly, and liver injury under high-fructose diet, while intestine-specific deletion has no effect. Inducible tissue-specific Fbp1 conditional knockout mice (liver vs. intestine), high-fructose diet challenge, metabolite (fructose-1-phosphate) measurement, liver histology and injury assays Endocrinology High 36964915
2020 CELF6 binds the 3'UTR of FBP1 mRNA and stabilizes it, increasing FBP1 protein expression and suppressing triple-negative breast cancer progression. Luciferase reporter assay (3'UTR binding), RNA immunoprecipitation (RIP), RNA pull-down, CELF6 overexpression/knockdown with FBP1 rescue Breast cancer research and treatment Medium 32601971
2019 HSF2 interacts with EHMT2 (G9a) to epigenetically silence FBP1 expression in hepatocellular carcinoma, thereby promoting aerobic glycolysis and cell proliferation. Co-immunoprecipitation (HSF2-EHMT2), HSF2 knockdown/overexpression, glycolysis assays, FBP1 expression analysis American journal of cancer research Medium 31497345
2020 LOXL2 intracellular enzymatic activity (not extracellular) upregulates Snail expression, which represses FBP1, thereby enhancing glycolysis and HIF-1α/VEGF signaling in hepatocellular carcinoma cells. The catalytically inactive LOXL2(Y689F) mutant does not affect Snail or FBP1. LOXL2 wild-type vs. catalytic mutant (Y689F) overexpression, LOXL2 siRNA knockdown, Snail-FBP1 rescue epistasis, LOXL2 inhibitor (LOXL2-IN-1) treatment, HIF-1α/VEGF expression analysis Oncology reports Medium 32323822
2024 P4HA1 overexpression under hypoxia reduces intracellular α-ketoglutarate (α-KG) levels (by consuming α-KG during collagen hydroxylation), which reduces TET2 protein levels and TET2 recruitment to the FBP1 promoter, resulting in decreased FBP1 expression and enhanced glycolysis to promote endothelial angiogenesis. α-KG measurement, TET2 protein analysis, ChIP-PCR (TET2 at FBP1 promoter), P4HA1 overexpression/knockdown, FBP1 expression rescue, angiogenesis assays in vitro and HLI mouse model Journal of translational medicine Medium 38238754
2018 FBP1 (gluconeogenic enzyme) inhibits HIF-1α protein expression and reduces transcription of HIF-1α target genes (PDK1, LDHA, GLUT1, VEGF) in basal-like breast cancer cells under hypoxia. ChIP demonstrated FBP1 occupancy at hypoxia response elements (HREs) in the PDK1 promoter. FBP1 lentiviral overexpression, Western blot (HIF-1α protein), RT-qPCR (HIF-1α target genes), chromatin immunoprecipitation (FBP1 at HRE of PDK1), glycolysis and cell growth assays Neoplasma Medium 28485159
2023 FOXP2 suppresses transcription of KDM5A (a histone demethylase), which blocks KDM5A-induced H3K4me3 demethylation at the FBP1 promoter, thereby increasing FBP1 expression and inhibiting the Warburg effect in HCC cells. ChIP (H3K4me3 at FBP1 promoter), FOXP2 and KDM5A gain/loss-of-function, FBP1 expression rescue, glycolysis assays, xenograft models Environmental toxicology Medium 37713600
2022 Retinoic acid (RA) activates FBP1 transcription via retinoic acid receptor (RAR) binding to the FBP1 gene (ChIP-PCR validated), upregulating FBP1 to suppress glycolysis and inhibit angiogenesis in human embryonic stem cell-derived endothelial cells. Silencing FBP1 reverses RA-induced angiogenesis inhibition. ChIP-PCR (RAR at FBP1 promoter), FBP1 knockdown/pharmacological inhibition, RAR inhibitor (BMS493), RNA sequencing, angiogenesis assays (proliferation, migration, tube formation) Stem cell research & therapy Medium 35672803
2020 GATA4 interacts physically with FBP1 protein (identified by immunoprecipitation-mass spectrometry) and positively regulates FBP1 expression in dental pulp stem cells (DPSCs). GATA4 promotes gluconeogenesis via FBP1; loss of GATA4 decreases FBP1 expression, increases glucose consumption and lactate production. Co-immunoprecipitation-mass spectrometry (GATA4-FBP1 interaction), GATA4 knockdown/overexpression, FBP1 knockdown, glucose/lactate metabolic assays, in vivo lentiviral GATA4 overexpression in mouse root International journal of biological sciences Medium 31892855
2021 In AML, Evi1 transcription factor directly interacts with the enhancer region of Fbp1 and upregulates its transcription. Fbp1 upregulation activates the pentose phosphate pathway in Evi1-driven leukemia, and pharmacological or shRNA-mediated Fbp1 inhibition selectively suppresses Evi1-driven leukemogenesis. ChIP (Evi1 at Fbp1 enhancer), transcriptomic and metabolomic profiling, Fbp1 shRNA knockdown, pharmacological Fbp1 inhibition, secondary transplantation leukemia mouse model Cancer science Medium 34363719
1991 In S. pombe, glucose repression of fbp1 transcription is mediated through the cAMP-PKA signaling pathway; git2/cyr1 (adenylate cyclase) is required for this repression, and exogenous cAMP restores repression in git mutants. The pathway is independent of ras1 and acts through activation of cAMP-dependent protein kinase. Genetic epistasis analysis with git mutants, fbp1-lacZ/fbp1-ura4 reporter fusions, exogenous cAMP supplementation, adenylate cyclase activity assays, intragenic complementation analysis Genes & development High 1849107
1994 In S. pombe, gpa2 (git8) encodes a Gα-protein subunit that partially regulates adenylate cyclase (Cyr1/Git2) activity for glucose repression of fbp1 transcription. Git3 and git5 act in concert with or independently from gpa2 to regulate adenylate cyclase. Gene identity mapping (git8=gpa2), fbp1-lacZ reporter assays, genetic epistasis (git3/git5 combined with gpa2 deletions), high-copy suppression Genetics Medium 8001792
2000 In S. pombe, fbp1 transcription is antagonistically regulated at two upstream activation sites (UAS1, UAS2) by PKA and MAPK pathways. UAS1 binds the atf1-pcr1 heterodimeric activator; MAPK positively and PKA negatively regulate atf1 binding at UAS1. UAS2 is bound by activators and repressors regulated by both pathways but does not involve atf1. Deletion analysis defining UAS1 and UAS2, gel-shift/EMSA identifying atf1-pcr1 at UAS1, fbp1 promoter-reporter constructs, PKA and MAPK mutant analysis Molecular and cellular biology High 10938120
2001 In S. pombe, two redundant Tup1p-like corepressors (Tup11 and Tup12) repress fbp1 transcription downstream of PKA; double deletion causes ~100-fold increase in fbp1-lacZ expression. The CCAAT-binding factor subunit Php5 activates fbp1 transcription in parallel to atf1-pcr1. cDNA library screen, tup11/tup12 double deletion analysis, fbp1-lacZ reporter assays, genetic epistasis with atf1/spc1 Genetics Medium 11238405
2003 In S. pombe, Tup11/Tup12 corepressors repress chromatin remodeling at two CRE-related regulatory elements in the fbp1+ promoter. Under derepressed conditions, chromatin is remodeled coordinately with transcriptional activation. Tup11/Tup12 deletion recapitulates the open chromatin state even under repressed conditions. Rst2 (a cAMP-PKA-controlled transcription factor) antagonizes Tup11/Tup12 chromatin repression. Chromatin immunoprecipitation (MNase sensitivity/nucleosome mapping), tup11/tup12 double deletion, rst2 deletion, chromatin structure analysis under repressed vs. derepressed conditions Genetics Medium 14573465
1985 The S. cerevisiae FBP1 gene encodes fructose bisphosphatase; disruption by transplacement creates a hexose auxotroph. FBP1 mRNA (~1350 nt) is glucose-repressible. The cloned gene confers fructose bisphosphatase activity in E. coli sensitive to fructose 2,6-bisphosphate inhibition. Gene cloning by complementation, transplacement disruption, Northern blot, enzymatic activity assay in E. coli, antibody precipitation Journal of molecular biology High 3003364
1995 The human FBP1 gene encodes fructose-1,6-bisphosphatase (EC 3.1.3.11), which catalyzes hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate and inorganic phosphate. The gene contains seven exons spanning >31 kb and is localized to chromosome 9q22.2-q22.3 by FISH. Gene cloning and structural characterization, fluorescence in situ hybridization (FISH), mutational screening by DNA sequencing, exon-intron mapping Genomics High 7558035

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Loss of FBP1 by Snail-mediated repression provides metabolic advantages in basal-like breast cancer. Cancer cell 669 23453623
2018 Dysfunction of Natural Killer Cells by FBP1-Induced Inhibition of Glycolysis during Lung Cancer Progression. Cell metabolism 300 30033198
2020 FBP1 loss disrupts liver metabolism and promotes tumorigenesis through a hepatic stellate cell senescence secretome. Nature cell biology 175 32367049
1991 Glucose repression of transcription of the Schizosaccharomyces pombe fbp1 gene occurs by a cAMP signaling pathway. Genes & development 137 1849107
2011 Promoter hypermethylation mediated downregulation of FBP1 in human hepatocellular carcinoma and colon cancer. PloS one 129 22039417
2011 USP22 regulates cell proliferation by deubiquitinating the transcriptional regulator FBP1. EMBO reports 118 21779003
1993 Petal and stamen formation in petunia is regulated by the homeotic gene fbp1. The Plant journal : for cell and molecular biology 112 8106081
2017 MAGE-TRIM28 complex promotes the Warburg effect and hepatocellular carcinoma progression by targeting FBP1 for degradation. Oncogenesis 104 28394358
1990 Isolation and characterization of mutants constitutive for expression of the fbp1 gene of Schizosaccharomyces pombe. Genetics 91 2157626
2017 Inhibiting histone deacetylases suppresses glucose metabolism and hepatocellular carcinoma growth by restoring FBP1 expression. Scientific reports 89 28262837
2018 HMGB2 is associated with malignancy and regulates Warburg effect by targeting LDHB and FBP1 in breast cancer. Cell communication and signaling : CCS 75 29463261
2003 Spatial and temporal expression of folate-binding protein 1 (Fbp1) is closely associated with anterior neural tube closure in mice. Developmental dynamics : an official publication of the American Association of Anatomists 72 12508232
2015 NPM1 activates metabolic changes by inhibiting FBP1 while promoting the tumorigenicity of pancreatic cancer cells. Oncotarget 68 26068981
2004 Structural and functional dissection of a conserved destabilizing element of cyclo-oxygenase-2 mRNA: evidence against the involvement of AUF-1 [AU-rich element/poly(U)-binding/degradation factor-1], AUF-2, tristetraprolin, HuR (Hu antigen R) or FBP1 (far-upstream-sequence-element-binding protein 1). The Biochemical journal 68 14594446
2000 Protein kinase A and mitogen-activated protein kinase pathways antagonistically regulate fission yeast fbp1 transcription by employing different modes of action at two upstream activation sites. Molecular and cellular biology 68 10938120
1994 The ecdysone response enhancer of the Fbp1 gene of Drosophila melanogaster is a direct target for the EcR/USP nuclear receptor. Molecular and cellular biology 62 8007953
2001 Transcriptional regulators of the Schizosaccharomyces pombe fbp1 gene include two redundant Tup1p-like corepressors and the CCAAT binding factor activation complex. Genetics 61 11238405
1995 Human fructose-1,6-bisphosphatase gene (FBP1): exon-intron organization, localization to chromosome bands 9q22.2-q22.3, and mutation screening in subjects with fructose-1,6-bisphosphatase deficiency. Genomics 60 7558035
2015 Down-regulation of FBP1 by ZEB1-mediated repression confers to growth and invasion in lung cancer cells. Molecular and cellular biochemistry 57 26546081
2020 E3 ubiquitin ligase UBR5 promotes pancreatic cancer growth and aerobic glycolysis by downregulating FBP1 via destabilization of C/EBPα. Oncogene 54 33122826
2011 The F-Box protein Fbp1 regulates sexual reproduction and virulence in Cryptococcus neoformans. Eukaryotic cell 54 21478432
2008 The FUSE binding proteins FBP1 and FBP3 are potential c-myc regulators in renal, but not in prostate and bladder cancer. BMC cancer 53 19087307
1992 Regulatory regions in the yeast FBP1 and PCK1 genes. FEBS letters 52 1327878
2018 CBX3 promotes proliferation and regulates glycolysis via suppressing FBP1 in pancreatic cancer. Biochemical and biophysical research communications 51 29678579
2018 The FOXC1/FBP1 signaling axis promotes colorectal cancer proliferation by enhancing the Warburg effect. Oncogene 51 30171256
2017 Loss of FBP1 facilitates aggressive features of hepatocellular carcinoma cells through the Warburg effect. Carcinogenesis 51 27742690
1994 Glucose repression of fbp1 transcription of Schizosaccharomyces pombe is partially regulated by adenylate cyclase activation by a G protein alpha subunit encoded by gpa2 (git8). Genetics 49 8001792
2021 FBP1 regulates proliferation, metastasis, and chemoresistance by participating in C-MYC/STAT3 signaling axis in ovarian cancer. Oncogene 48 34363022
1985 Fructose bisphosphatase of Saccharomyces cerevisiae. Cloning, disruption and regulation of the FBP1 structural gene. Journal of molecular biology 48 3003364
2013 Fbp1-mediated ubiquitin-proteasome pathway controls Cryptococcus neoformans virulence by regulating fungal intracellular growth in macrophages. Infection and immunity 47 24478071
2018 Restoration of FBP1 suppressed Snail-induced epithelial to mesenchymal transition in hepatocellular carcinoma. Cell death & disease 45 30429463
2019 Long noncoding RNA DANCR regulates proliferation and migration by epigenetically silencing FBP1 in tumorigenesis of cholangiocarcinoma. Cell death & disease 44 31383847
2019 Decreased FBP1 expression rewires metabolic processes affecting aggressiveness of glioblastoma. Oncogene 44 31444412
1991 Regions in the promoter of the yeast FBP1 gene implicated in catabolite repression may bind the product of the regulatory gene MIG1. FEBS letters 43 1657641
2021 TRIM47 accelerates aerobic glycolysis and tumor progression through regulating ubiquitination of FBP1 in pancreatic cancer. Pharmacological research 42 33529753
2018 The F-Box Protein Fbp1 Shapes the Immunogenic Potential of Cryptococcus neoformans. mBio 41 29317510
2003 Fission yeast Tup1-like repressors repress chromatin remodeling at the fbp1+ promoter and the ade6-M26 recombination hotspot. Genetics 41 14573465
2019 USP44 suppresses pancreatic cancer progression and overcomes gemcitabine resistance by deubiquitinating FBP1. American journal of cancer research 40 31497353
2025 FBP1 controls liver cancer evolution from senescent MASH hepatocytes. Nature 38 39743585
2018 FBP1 loss contributes to BET inhibitors resistance by undermining c-Myc expression in pancreatic ductal adenocarcinoma. Journal of experimental & clinical cancer research : CR 38 30201002
2017 FBP1 modulates cell metabolism of breast cancer cells by inhibiting the expression of HIF-1α. Neoplasma 35 28485159
2017 Snail Enhances Glycolysis in the Epithelial-Mesenchymal Transition Process by Targeting FBP1 in Gastric Cancer. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 32 28848200
2018 Forced overexpression of FBP1 inhibits proliferation and metastasis in cholangiocarcinoma cells via Wnt/β-catenin pathway. Life sciences 30 30193944
2021 LncRNA MT1JP plays a protective role in intrahepatic cholangiocarcinoma by regulating miR-18a-5p/FBP1 axis. BMC cancer 29 33557774
2009 Novel FBP1 gene mutations in Arab patients with fructose-1,6-bisphosphatase deficiency. European journal of pediatrics 28 19259699
1995 Analysis of positive elements sensitive to glucose in the promoter of the FBP1 gene from yeast. The Journal of biological chemistry 28 7759539
1995 Functional interaction between the homeotic genes fbp1 and pMADS1 during petunia floral organogenesis. The Plant cell 28 7780304
2000 Differences in regulation of yeast gluconeogenesis revealed by Cat8p-independent activation of PCK1 and FBP1 genes in Kluyveromyces lactis. Molecular & general genetics : MGG 27 11016849
2021 FBP1 enhances the radiosensitivity by suppressing glycolysis via the FBXW7/mTOR axis in nasopharyngeal carcinoma cells. Life sciences 26 34298040
2019 HSF2 regulates aerobic glycolysis by suppression of FBP1 in hepatocellular carcinoma. American journal of cancer research 26 31497345
2024 The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7. Cardiovascular diabetology 25 38195542
2020 LOXL2 upregulates hypoxia‑inducible factor‑1α signaling through Snail‑FBP1 axis in hepatocellular carcinoma cells. Oncology reports 25 32323822
2016 The tomato floral homeotic protein FBP1-like gene, SlGLO1, plays key roles in petal and stamen development. Scientific reports 24 26842499
2021 Deubiquitination of FBP1 by USP7 blocks FBP1-DNMT1 interaction and decreases the sensitivity of pancreatic cancer cells to PARP inhibitors. Molecular oncology 23 34854226
2019 GSK343 induces programmed cell death through the inhibition of EZH2 and FBP1 in osteosarcoma cells. Cancer biology & therapy 23 31651209
2021 Gastric cancer mesenchymal stem cells inhibit natural killer cell function by up-regulating FBP1. Central-European journal of immunology 22 35125940
2019 The involvement of FBP1 in prostate cancer cell epithelial mesenchymal transition, invasion and metastasis by regulating the MAPK signaling pathway. Cell cycle (Georgetown, Tex.) 21 31448674
2018 Significance of Methylation of FBP1 Gene in Non-Small Cell Lung Cancer. BioMed research international 21 29984231
2017 Increased miR-21a provides metabolic advantages through suppression of FBP1 expression in non-small cell lung cancer cells. American journal of cancer research 21 29218237
2024 FBP1 orchestrates keratinocyte proliferation/differentiation and suppresses psoriasis through metabolic control of histone acetylation. Cell death & disease 20 38834617
2022 PTEN loss promotes Warburg effect and prostate cancer cell growth by inducing FBP1 degradation. Frontiers in oncology 20 36237339
2018 CCAAT-enhancer binding protein-α (C/EBPα) and hepatocyte nuclear factor 4α (HNF4α) regulate expression of the human fructose-1,6-bisphosphatase 1 (FBP1) gene in human hepatocellular carcinoma HepG2 cells. PloS one 20 29566023
2017 Invalidation of mitophagy by FBP1-mediated repression promotes apoptosis in breast cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 20 28653874
1998 Transcription termination downstream of the Saccharomyces cerevisiae FBP1 [changed from FPB1] poly(A) site does not depend on efficient 3'end processing. RNA (New York, N.Y.) 20 9510332
2020 Knockdown of FBP1 enhances radiosensitivity in prostate cancer cells by activating autophagy. Neoplasma 19 32453596
2020 CELF6 modulates triple-negative breast cancer progression by regulating the stability of FBP1 mRNA. Breast cancer research and treatment 19 32601971
2020 UCP1 regulates ALDH-positive breast cancer stem cells through releasing the suppression of Snail on FBP1. Cell biology and toxicology 18 32472219
2017 Interplay between chromatin modulators and histone acetylation regulates the formation of accessible chromatin in the upstream regulatory region of fission yeast fbp1. Genes & genetic systems 18 28674280
2001 Regulatory elements in the FBP1 promoter respond differently to glucose-dependent signals in Saccharomyces cerevisiae. The Biochemical journal 18 11563983
2024 Hypoxia-induced P4HA1 overexpression promotes post-ischemic angiogenesis by enhancing endothelial glycolysis through downregulating FBP1. Journal of translational medicine 17 38238754
2023 AF9 sustains glycolysis in colorectal cancer via H3K9ac-mediated PCK2 and FBP1 transcription. Clinical and translational medicine 17 37565737
1993 In vivo functional characterization of an ecdysone response enhancer in the proximal upstream region of the Fbp1 gene of D. melanogaster. Mechanisms of development 17 8155577
2023 GBE1 Promotes Glioma Progression by Enhancing Aerobic Glycolysis through Inhibition of FBP1. Cancers 16 36900384
2020 Loss of FBP1 promotes proliferation, migration, and invasion by regulating fatty acid metabolism in esophageal squamous cell carcinoma. Aging 16 33232284
2024 FBP1 inhibits NSCLC stemness by promoting ubiquitination of Notch1 intracellular domain and accelerating degradation. Cellular and molecular life sciences : CMLS 15 38349431
2022 Retinoic acid inhibits the angiogenesis of human embryonic stem cell-derived endothelial cells by activating FBP1-mediated gluconeogenesis. Stem cell research & therapy 15 35672803
2022 FBP1 /miR-24-1/enhancer axis activation blocks renal cell carcinoma progression via Warburg effect. Frontiers in oncology 15 35978816
2020 FBP1 binds to the bromodomain of BRD4 to inhibit pancreatic cancer progression. American journal of cancer research 15 32195024
2018 miR-517a promotes Warburg effect in HCC by directly targeting FBP1. OncoTargets and therapy 15 30519044
2014 FBP1 and p27kip1 expression after sciatic nerve injury: implications for Schwann cells proliferation and differentiation. Journal of cellular biochemistry 15 23939805
2023 Piperlongumine based nanomedicine impairs glycolytic metabolism in triple negative breast cancer stem cells through modulation of GAPDH & FBP1. Phytomedicine : international journal of phytotherapy and phytopharmacology 13 38091824
2020 The CDK4/6 inhibitor PD0332991 stabilizes FBP1 by repressing MAGED1 expression in pancreatic ductal adenocarcinoma. The international journal of biochemistry & cell biology 13 32987196
2019 lncRNA transcriptional initiation induces chromatin remodeling within a limited range in the fission yeast fbp1 promoter. Scientific reports 13 30670704
2017 FBP1 expression is associated with basal-like breast carcinoma. Oncology letters 13 28529559
2015 The F-box protein Fbp1 functions in the invasive growth and cell wall integrity mitogen-activated protein kinase (MAPK) pathways in Fusarium oxysporum. Molecular plant pathology 13 25808603
1998 Functional analysis of upstream activating elements in the promoter of the FBP1 gene from Saccharomyces cerevisiae. Current genetics 13 9644203
2022 Vitamin D activates FBP1 to block the Warburg effect and modulate blast metabolism in acute myeloid leukemia. Biomarker research 12 35366947
2018 FBP1 promotes ovarian cancer development through the acceleration of cell cycle transition and metastasis. Oncology letters 12 30008853
2001 Elements from the cAMP signaling pathway are involved in the control of expression of the yeast gluconeogenic gene FBP1. FEBS letters 12 11602258
1993 Deletion scanning of the regulatory sequences of the Fbp1 gene of Drosophila melanogaster using P transposase-induced deficiencies. Genetics 12 8293980
2022 FBP1 knockdown decreases ovarian cancer formation and cisplatin resistance through EZH2-mediated H3K27me3. Bioscience reports 11 36000567
2022 FBP1 induced by β-elemene enhances the sensitivity of gefitinib in lung cancer. Thoracic cancer 11 36525508
2021 Evi1 upregulates Fbp1 and supports progression of acute myeloid leukemia through pentose phosphate pathway activation. Cancer science 11 34363719
2020 GATA Binding Protein 4 Regulates Tooth Root Dentin Development via FBP1. International journal of biological sciences 11 31892855
2023 Development of a Heat-Killed fbp1 Mutant Strain as a Therapeutic Agent To Treat Invasive Cryptococcus Infection. Microbiology spectrum 10 36719231
2023 Hepatic but not Intestinal FBP1 Is Required for Fructose Metabolism and Tolerance. Endocrinology 10 36964915
2022 FBP1-Altered Carbohydrate Metabolism Reduces Leukemic Viability through Activating P53 and Modulating the Mitochondrial Quality Control System In Vitro. International journal of molecular sciences 10 36232688
2017 FBP1 is highly expressed in human hypertrophic scars and increases fibroblast proliferation, apoptosis, and collagen expression. Connective tissue research 10 28362515
2023 Immunodeficiency with susceptibility to lymphoma with complex genotype affecting energy metabolism (FBP1, ACAD9) and vesicle trafficking (RAB27A). Frontiers in immunology 9 37388727
2023 FOXP2 suppresses the proliferation, invasion, and aerobic glycolysis of hepatocellular carcinoma cells by regulating the KDM5A/FBP1 axis. Environmental toxicology 9 37713600

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