Affinage

FOXK1

Forkhead box protein K1 · UniProt P85037

Length
733 aa
Mass
75.5 kDa
Annotated
2026-06-09
100 papers in source corpus 42 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FOXK1 is a forkhead/winged-helix transcription factor and FHA-domain protein that couples nutrient and growth-factor signaling to a transcriptional program governing cellular metabolism, cell-cycle progression, and chromatin state (PMID:30700909, PMID:30952843). Its activity is controlled chiefly by regulated nuclear access: active mTORC1 suppresses GSK3-dependent phosphorylation of FOXK1, preventing 14-3-3 binding and nuclear exclusion, while PP2A-B56 dephosphorylates nuclear FOXK1 to license its transcriptional output, so that insulin/Akt-mTOR signaling drives FOXK1 into the nucleus reciprocally to FoxO1 export (PMID:29861159, PMID:29845697, PMID:30952843). Once nuclear, FOXK1 (with FOXK2) directly transactivates glycolytic enzyme genes (HK2, PFK, PKM, LDHA) and pyruvate dehydrogenase kinases while suppressing pyruvate dehydrogenase phosphatase, diverting pyruvate to lactate and enforcing aerobic glycolysis—an axis it uses in hepatocytes, osteoblasts, and cardiomyocytes (PMID:30700909, PMID:39232134, PMID:40128196). FOXK1 promotes cell-cycle progression by repressing the CDK inhibitor p21 (genetically epistatic in myogenic progenitors) and by directly activating cell-cycle drivers including CDC25A, CDK4, CCNB1, and CDK1 (PMID:12446708, PMID:29050292, PMID:37173384, PMID:40128196). FOXK1 is also a chromatin-regulatory factor: it is an integral subunit of the BAP1 PR-DUB complex (with HCFC1, OGT, and ASXL proteins), recruiting BAP1 to chromatin to remove H2AK119ub1, and O-GlcNAcylation of FOXK1 peaking at G1/S is required for BAP1 co-recruitment and E2F target activation (PMID:32747411, PMID:40593803). It additionally nucleates corepressor complexes (Sin3, NCoR/SIN3A, REST/CoREST) to repress target genes and interacts with 53BP1 to inhibit NHEJ and bias repair toward homologous recombination (PMID:22476904, PMID:39094826, PMID:38238876, PMID:32783940). Protein levels are stabilized by deubiquitination (USP28) and by HDAC3, which protects FOXK1 from lysosomal degradation to sustain STAT1/2 expression in antiviral immunity (PMID:39983825, PMID:35081346). FOXK1 has essential developmental roles in myogenic progenitor cycling, cardiogenesis through repression of Wnt/β-catenin, osteoblast bone formation, and adipogenesis via Pparγ2 (PMID:12446708, PMID:37036809, PMID:39232134, PMID:37889840).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2002 High

    Established FOXK1 as a required driver of progenitor cell-cycle progression and placed a defined cell-cycle inhibitor downstream of it, the first genetic dissection of FOXK1 function.

    Evidence Foxk1 knockout and Foxk1/p21CIP double-knockout epistasis with cell-cycle and regeneration readouts in mice

    PMID:12446708

    Open questions at the time
    • Did not establish whether p21 repression is direct DNA binding versus indirect
    • Restricted to myogenic progenitors
  2. 2007 High

    Defined upstream transcriptional control of the Foxk1 gene and identified FOXK1 as an SRF-dependent transcriptional repressor, framing its dual coactivator/corepressor behavior.

    Evidence Sox15/Fhl3 promoter studies with transgenic reporter and ChIP; SRF Co-IP and ChIP at SM alpha-actin/PPGB promoters

    PMID:17363903 PMID:17670796

    Open questions at the time
    • Mechanism converting FOXK1 between activator and repressor not defined
    • Cofactor requirements at SRF sites unresolved
  3. 2012 High

    Identified the corepressor partners and protein interactions through which FOXK1 represses myogenic differentiation and promotes proliferation, mapping a partner network (Sin3, FHL2, FOXO4, MEF2).

    Evidence Yeast two-hybrid, GST pull-down, domain mapping, Co-IP, and reporter assays with knockdown phenotypes in C2C12 cells

    PMID:20013826 PMID:22476904 PMID:22956541

    Open questions at the time
    • Genome-wide target sets not defined
    • Several interactions characterized only in myogenic context
  4. 2010 High

    Showed FOXK1/K2 are shared targets of viral oncoproteins via a conserved Ser/Thr motif, implicating them in suppression of cell transformation and foreshadowing FHA-domain recognition of phosphomotifs.

    Evidence TAP-MS, Co-IP, motif mutagenesis, and transformation assays with adenovirus E1A and beta-HPV E6

    PMID:20053746

    Open questions at the time
    • Endogenous phosphomotif partners not identified at this stage
    • Transcriptional consequences of viral engagement undefined
  5. 2018 High

    Resolved how nutrient/growth-factor signaling controls FOXK1, defining the mTORC1–GSK3–14-3-3 and PP2A-B56 circuit that gates its nuclear localization and transcriptional activity.

    Evidence Phosphoproteomics, 14-3-3 Co-IP, nuclear/cytoplasmic fractionation, ChIP, mutagenesis, and PP2A-B56 knockdown rescue

    PMID:29186685 PMID:29845697 PMID:29861159

    Open questions at the time
    • Full set of GSK3/PP2A target residues incompletely mapped
    • How dephosphorylation alters DNA binding affinity mechanistically not resolved
  6. 2019 High

    Established FOXK1/K2 as master inducers of aerobic glycolysis and showed insulin-driven nuclear translocation reciprocal to FoxO1, connecting signaling input to a metabolic transcriptional output.

    Evidence ChIP, RNA-seq, reporter assays, enzyme activity, metabolic flux, and knockdown/overexpression in cell lines, primary cells, and in vivo

    PMID:30700909 PMID:30952843

    Open questions at the time
    • Co-activators required for glycolytic gene activation not fully defined
    • Relationship between metabolic and cell-cycle gene programs left open
  7. 2020 High

    Defined FOXK1 as a chromatin-regulatory factor by establishing it as an integral PR-DUB subunit that recruits BAP1 to remove H2AK119ub1, and revealed an ASXL1 mutation that disrupts this recruitment in leukemia.

    Evidence Co-IP, ChIP-seq, H2AK119ub1 ChIP, RNA-seq, and FOXK1/2 and ASXL knockouts in ES cells; allele-specific ASXL1 deletion

    PMID:32683582 PMID:32747411

    Open questions at the time
    • Determinants of PR-DUB targeting to specific loci incompletely defined
    • ASXL1 finding rests on single-lab allele-specific experiments
  8. 2020 High

    Extended FOXK1 function into genome stability, showing a cell-cycle/DNA-damage-regulated interaction with 53BP1 that biases double-strand-break repair and confers PARP-inhibitor resistance.

    Evidence Co-IP, proximity ligation, laser micro-irradiation, telomere fusion, HR/NHEJ and PARPi sensitivity assays

    PMID:32783940

    Open questions at the time
    • Whether the 53BP1 effect requires FOXK1 DNA binding or is purely protein-scaffolding unresolved
    • Generality across cell types beyond BRCA1-deficient models untested
  9. 2022 High

    Showed FOXK1 stability is regulated by HDAC3, which protects it from lysosomal degradation to sustain STAT1/2 transcription and antiviral immunity, adding a degradation-control layer.

    Evidence Co-IP, ChIP, HDAC3/FOXK1 knockout macrophages, viral infection and lysosomal-inhibitor experiments

    PMID:35081346

    Open questions at the time
    • E3 ligase routing FOXK1 to lysosomal degradation not identified
    • Whether HDAC3 catalytic activity is required unclear
  10. 2023 High

    Defined developmental and regenerative roles of FOXK1 in heart and bone, linking its glycolytic and cell-cycle programs to cardiac progenitor specification, cardiomyocyte proliferation, and osteoblast bone formation.

    Evidence Foxk1 KO embryoid bodies and cardiomyocyte/preosteoblast conditional KO with RNA-seq, ATAC-seq, CUT&Tag, ChIP, glycolysis and 2-DG rescue, and in vivo cardiac/bone phenotypes

    PMID:37036809 PMID:39232134 PMID:40128196

    Open questions at the time
    • Direct targets mediating Wnt/β-catenin repression in cardiogenesis not fully enumerated
    • Crosstalk between metabolic and cell-cycle target sets in vivo not dissected
  11. 2024 High

    Identified O-GlcNAcylation as the modification gating FOXK1's chromatin output, required for BAP1 co-recruitment and E2F target activation and linking insulin resistance to FOXK1-driven oncogenesis.

    Evidence O-GlcNAc mass spectrometry, site mutagenesis, OGT inhibition, ChIP-seq, H2AK119ub ChIP, BAP1 Co-IP, transformation and xenograft assays

    PMID:38463952 PMID:40593803

    Open questions at the time
    • Interplay between O-GlcNAcylation and the phospho-regulated nuclear localization switch not integrated
    • Whether all FOXK1 functions depend on O-GlcNAcylation unknown
  12. 2024 Medium

    Expanded the FOXK1 corepressor repertoire (NCoR/SIN3A, NuRD, REST/CoREST) and showed repression of circadian and apoptotic gene programs in breast cancer, with USP28-mediated deubiquitination as an additional stabilization route.

    Evidence MS-based complex identification, ChIP-seq, Co-IP, TUNEL/colony assays, xenografts; in vitro ubiquitination and USP28 knockdown

    PMID:38238876 PMID:39094826 PMID:39983825

    Open questions at the time
    • Determinants selecting among multiple corepressor complexes at given loci unknown
    • Several interactions rest on single-lab Co-IP/ChIP

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the phospho-regulated nuclear-access switch, O-GlcNAc-dependent chromatin recruitment, and the choice between coactivator versus corepressor complexes are integrated into a single context-specific FOXK1 output remains unresolved.
  • No unified model coupling PTM state to target selection
  • Structural basis of FHA-domain phosphomotif recognition of endogenous partners not defined
  • In vivo causal hierarchy among metabolic, cell-cycle, and chromatin functions unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 3 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3 GO:0005829 cytosol 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-1640170 Cell Cycle 4 R-HSA-1430728 Metabolism 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-162582 Signal Transduction 2 R-HSA-4839726 Chromatin organization 2 R-HSA-73894 DNA Repair 1
Partners
53BP1ASXL1BAP1FHL2FOXK2HDAC3SRFUSP28
Complex memberships
BAP1 PR-DUB complexNCoR/SIN3A corepressor complexREST/CoREST complex

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 mTORC1 suppresses GSK3-dependent phosphorylation of FOXK1; when mTORC1 is inhibited, GSK3 phosphorylates FOXK1, triggering 14-3-3 binding, reduced DNA binding, and nuclear exclusion of FOXK1. Active mTORC1 thus keeps FOXK1 nuclear and transcriptionally active, driving expression of glycolytic and HIF-1α-dependent anabolic genes. Phosphoproteomics, 14-3-3 co-IP, nuclear/cytoplasmic fractionation, ChIP, gene-expression analysis, GSK3 inhibitor and mTOR inhibitor treatments, mutagenesis of phosphorylation sites Molecular cell High 29861159
2018 PP2A regulatory subunit B56 shuttles between nucleus and cytoplasm and is required for mTORC1-dependent dephosphorylation of nuclear FOXK1, providing the mechanistic link between lysosomal mTORC1 activity and nuclear FOXK1 regulation. Nuclear-cytoplasmic fractionation, PP2AB56 knockdown, co-immunoprecipitation, phosphorylation assays Genes to cells Medium 29845697
2017 mTORC1 activation induces PP2A-mediated dephosphorylation of FOXK1, leading to its nuclear accumulation and direct transactivation of the CCL2 gene independently of NF-κB, thereby promoting recruitment of tumor-associated macrophages. Multiple phosphoproteomics approaches, ChIP, luciferase reporter assay, FOXK1 knockdown/overexpression, rapamycin treatment, in vivo macrophage accumulation assay Cell reports High 29186685
2019 FOXK1 and FOXK2 induce aerobic glycolysis by transcriptionally upregulating glycolytic enzymes (HK2, PFK, PKM, LDHA) and pyruvate dehydrogenase kinases 1 and 4 while suppressing pyruvate dehydrogenase phosphatase 1, leading to increased phosphorylation of the PDC E1α subunit and diversion of pyruvate to lactate rather than mitochondrial oxidation. ChIP, luciferase reporter, RNA-seq, FOXK1/K2 knockdown and overexpression in cell lines and primary human cells, in vivo metabolic measurements, enzyme activity assays Nature High 30700909
2019 Following insulin stimulation, FOXK1 and FOXK2 translocate from the cytoplasm to the nucleus (reciprocal to FoxO1 nuclear export) in an Akt-mTOR-dependent manner; basal cytoplasmic retention requires GSK3. Knockdown of FoxK1/K2 in liver cells downregulates cell-cycle and lipid-metabolism genes and alters mitochondrial fatty acid metabolism. Immunofluorescence localization, nuclear/cytoplasmic fractionation, Akt/mTOR and GSK3 inhibitor treatments, siRNA knockdown, RNA-seq, metabolic flux analysis Nature communications High 30952843
2002 Foxk1 is required for myogenic progenitor cell (MPC) cycle progression; Foxk1-null mice show G0/G1 arrest and elevated p21CIP expression. Genetic ablation of p21CIP in Foxk1-/- mice fully restores MPC number, cell cycle progression, skeletal muscle regeneration, and growth, placing p21CIP downstream of FOXK1. Foxk1 knockout mice, combinatorial Foxk1/p21CIP double-knockout epistasis, cell cycle analysis, immunostaining, histology The Journal of biological chemistry High 12446708
2007 Sox15 binds to an evolutionarily conserved site in the Foxk1 promoter and recruits Fhl3 to transcriptionally coactivate Foxk1 gene expression in myogenic progenitor cells. Sox15 knockout mice display decreased Foxk1 expression and impaired skeletal muscle regeneration. Transgenic reporter assays (4.6 kb Foxk1 promoter-LacZ), ChIP, Sox15 knockdown, Sox15 knockout mouse phenotyping The EMBO journal High 17363903
2012 FOXK1 physically interacts with both FOXO4 and MEF2, repressing their transcriptional activities; this repression promotes MPC proliferation and inhibits myogenic differentiation respectively. Co-IP, GST pull-down, luciferase transcriptional reporter assays, Foxk1 knockdown in C2C12 cells (cell cycle arrest), Foxk1 overexpression in C2C12CAR cells (impaired differentiation) Journal of cell science High 22956541
2010 The LIM-only protein Fhl2 interacts with Foxk1 through a yeast two-hybrid screen and GST pull-down, and in a dose-dependent manner promotes Foxk1-mediated transcriptional repression of Foxo4 activity. Fhl2 knockdown causes MPC cell cycle arrest; Fhl2-null mice have impaired skeletal muscle regeneration. Yeast two-hybrid screen, GST pull-down, transcriptional reporter assays, Fhl2 knockdown, Fhl2 knockout mice Stem cells High 20013826
2012 Sin3 (Sin3A and Sin3B) interacts with Foxk1; the Foxk1 N-terminal residues 1–40 (SID) bind the PAH2 domain of Sin3. Sin3A or Sin3B knockdown causes MPC cell cycle arrest and upregulates cell cycle inhibitor genes. Yeast two-hybrid screen, GST pull-down, domain-mapping mutagenesis, Sin3 knockdown with cell cycle analysis Molecular and cellular biochemistry Medium 22476904
2007 FOXK1 interacts with SRF in human cells; FOXK1 binding to the SM alpha-actin and PPGB promoters is dependent on SRF occupancy, and FOXK1 acts as a transcriptional repressor of these SRF target genes. Co-immunoprecipitation, ChIP, luciferase reporter assays, FOXK1 overexpression/knockdown Nucleic acids research Medium 17670796
2010 Adenovirus E1A C-terminus interacts with FOXK1/K2 via a Ser/Thr-containing motif; E1A mutants deficient in this interaction show enhanced cell proliferation and oncogenic transformation. Beta-HPV E6 proteins also interact with FOXK1/K2 through a similar motif and suppress E1A-induced transformation, indicating FOXK1/K2 as shared targets that suppress cell transformation. Tandem affinity purification, mass spectrometry, co-immunoprecipitation, mutagenesis of the Ser/Thr motif, cell transformation assays Journal of virology High 20053746
2020 FOXK1 and FOXK2 are integral components of the mammalian PR-DUB complex (containing BAP1, HCFC1, FOXK1/2, OGT, and ASXL1/2/3); FOXK1/2 and ASXL proteins mediate BAP1 recruitment to chromatin to remove H2AK119ub1 and maintain expression of metabolic and homeostatic genes. Co-IP, ChIP-seq, H2AK119ub1 ChIP, FOXK1/2 and ASXL knockouts in embryonic stem cells, RNA-seq Genome research High 32747411
2020 ASXL1 interacts with FOXK1 and FOXK2 to regulate a subset of FOXK1/K2 target genes (involved in glucose metabolism, oxygen sensing, JAK-STAT3 signaling). C-terminally truncated mutant ASXL1 (leukemia-associated) loses the ability to interact with FOXK1/K2, impairing BAP1-ASXL1-FOXK1/K2 target gene regulation. Co-IP, mass spectrometry, ChIP, gene expression analysis in ASXL1 heterozygous leukemia cells with specific deletion of mutant allele Protein & cell Medium 32683582
2020 FOXK1 associates with 53BP1, and this interaction is enhanced during S phase upon DNA damage in an ATM/CHK2-dependent manner. FOXK1-53BP1 interaction reduces 53BP1 association with its downstream effectors RIF1 and PTIP, thereby negatively regulating 53BP1 foci formation, impairing NHEJ and promoting HR. FOXK1 overexpression causes PARPi resistance in BRCA1-deficient cells. Co-IP, proximity ligation assay, laser micro-irradiation/live imaging, siRNA depletion, PARP inhibitor sensitivity assays, telomere fusion assay, cell cycle synchronization Cell reports High 32783940
2022 HDAC3 interacts with FOXK1, co-localizes with it at the promoters of STAT1 and STAT2, and protects FOXK1 from lysosomal degradation. This HDAC3-FOXK1 complex is required for STAT1/STAT2 expression and macrophage antiviral innate immunity. Co-IP, ChIP, HDAC3 and FOXK1 knockout macrophages, viral infection assays, lysosomal inhibitor experiments Cell reports High 35081346
2016 c-jun directly binds to and activates the human FOXK1 gene promoter, stimulating FOXK1 expression. TGF-β1 treatment also induces FOXK1 expression and EMT; siRNA-mediated repression of c-jun in FOXK1-overexpressing cells reverses EMT, proliferation, and metastatic phenotypes. Promoter reporter assay, ChIP, siRNA knockdown, in vivo orthotopic implantation Cell death & disease Medium 27882939
2018 FOXK1 physically interacts with Snail; Snail directly binds to and activates the FOXK1 gene promoter. FOXK1 in turn directly transactivates Cyr61, driving EMT-mediated invasion and metastasis in colorectal cancer. Luciferase reporter assay, ChIP, co-immunoprecipitation, siRNA knockdown, invasion assays, in vivo metastasis model Cellular physiology and biochemistry Medium 29794466
2016 FOXK1 physically interacts with FHL2 in colorectal cancer cells; co-expression of FOXK1 and FHL2 enhances cell proliferation and metastasis through EMT induction. siRNA-mediated repression of FHL2 in FOXK1-overexpressing cells reverses EMT and proliferative/metastatic phenotypes. Co-IP, immunofluorescence, shRNA knockdown, in vitro invasion assays, in vivo xenograft Oncogenesis Medium 27892920
2018 FOXK1 physically interacts with vimentin and stabilizes it; co-expression of FOXK1 and vimentin promotes EMT, migration, and invasion in gastric cancer. siRNA-mediated knockdown of vimentin in FOXK1-overexpressing cells reverses EMT and reduces invasion. Co-IP, western blot, immunofluorescence, siRNA knockdown, in vitro and in vivo invasion/metastasis assays Journal of molecular medicine Medium 30483822
2017 RUFY3 physically interacts with FOXK1 in colorectal cancer; siRNA repression of FOXK1 in RUFY3-overexpressing cells reverses EMT and metastatic phenotypes, placing FOXK1 downstream of RUFY3. Co-IP, immunofluorescence, siRNA knockdown, in vitro and in vivo invasion/metastasis assays Scientific reports Low 28623323
2020 Nuclear DLC1 interacts with FOXK1 (identified by mass spectrometry) and is retained in the nucleus through this interaction; together DLC1 and FOXK1 cooperate at the MMP9 promoter to activate MMP9 transcription and promote melanoma invasion. Mass spectrometry, Co-IP, RNA-seq, ChIP, FOXK1/DLC1 knockdown, invasion assays Oncogene Medium 32214200
2018 FOXK1 directly binds and activates the CCDC43 gene promoter; CCDC43 is required for FOXK1-mediated EMT and metastasis in colorectal cancer. Luciferase reporter assay, ChIP, siRNA knockdown, EMT markers, invasion assays in vitro and in vivo Cellular physiology and biochemistry Medium 30562730
2018 FOXK1 directly binds the Snail promoter and activates its transcription in glioblastoma cells, thereby promoting EMT and cell proliferation. Luciferase reporter assay, ChIP, FOXK1 knockdown/overexpression, cell cycle and invasion assays Experimental and therapeutic medicine Medium 29456714
2017 FOXK1 facilitates cell cycle progression in ovarian cancer by directly regulating p21 expression; ChIP and luciferase assays demonstrated FOXK1 binds the p21 promoter and suppresses its transcription, promoting S-phase entry. ChIP, luciferase reporter assay, colony formation, CCK-8, flow cytometry Oncotarget Medium 29050292
2023 FOXK1 directly activates CDC25A and CDK4 transcription by binding to their promoter regions in esophageal squamous cell carcinoma; this drives G1/S progression. Silencing FOXK1 increases radiosensitivity by impairing DNA damage repair and inducing G1 arrest. ChIP, luciferase reporter assay, FOXK1 knockdown/overexpression, γ-H2AX foci imaging, flow cytometry, colony survival assay Scientific reports Medium 37173384
2023 FOXK1 regulates cardiogenesis by repressing the Wnt/β-catenin signaling pathway; Foxk1 KO embryoid bodies show impaired cardiac progenitor specification, reduced cardiac gene program (RNA-seq), closed chromatin at cardiogenesis loci (ATAC-seq), and loss of cardiomyocyte contractility. Foxk1 KO ES cell-derived embryoid bodies, flow cytometry, RNA-seq, ATAC-seq, ChIP-qPCR, cardiac beating assay, immunohistochemistry Cardiovascular research High 37036809
2025 Foxk1 and Foxk2 directly activate CCNB1 and CDK1 transcription, forming a CCNB1/CDK1 complex that facilitates G2/M transition in cardiomyocytes; they also upregulate HIF1α to enhance glycolysis and the pentose phosphate pathway, supporting cardiomyocyte proliferation. Cardiomyocyte-specific KO impairs neonatal heart regeneration after MI; AAV9-mediated overexpression extends the proliferative window and enhances adult cardiac repair. Cardiomyocyte-specific KO mice, AAV9 overexpression, ChIP, RNA-seq, flow cytometry, MI model, cell cycle analysis Nature communications High 40128196
2024 Foxk1 directly binds promoter regions of glycolytic enzyme genes in osteoblasts (identified by CUT&Tag), and conditional Foxk1 KO in preosteoblasts reduces aerobic glycolysis, osteoblast differentiation, bone mass, and mechanical strength. Glycolysis inhibition by 2-DG blocks Foxk1-overexpression-induced osteoblast effects, confirming glycolysis as the mechanistic effector. Conditional Foxk1 KO mice, CUT&Tag, glycolysis assays, 2-DG inhibition, Osterix-Cre overexpression, bone histomorphometry Cell death and differentiation High 39232134
2024 FOXK1 is O-GlcNAcylated; this modification peaks at G1/S and is required for FOXK1 to promote E2F target gene transcription, cell proliferation, and cellular transformation. O-GlcNAcylation-defective FOXK1 shows reduced BAP1 recruitment to gene regulatory regions, accompanied by increased H2AK119ub and decreased H3K4me1, creating a repressive chromatin state. OGT-dependent O-GlcNAcylation is promoted by insulin resistance/nuclear OGT elevation. O-GlcNAc modification assay, OGT inhibition/knockdown, mutagenesis of O-GlcNAcylation sites, ChIP-seq, H2AK119ub ChIP, Co-IP with BAP1, cell transformation assays, xenograft Nature communications High 40593803
2024 FOXK1 O-GlcNAcylation (same finding as above, initially reported as preprint) co-opts BAP1 to the E2F pathway to promote oncogenesis; loss of O-GlcNAcylation reduces BAP1 occupancy, increases H2AK119ub, and impairs E2F target gene expression. O-GlcNAc mass spectrometry, site mutagenesis, ChIP-seq, Co-IP, cell proliferation/transformation assays bioRxivpreprint High 38463952
2023 FoxK1 binds to the Pparγ2 promoter and stimulates its transcriptional activity in mesenchymal progenitor cells; adipogenic stimulation induces nuclear translocation of Foxk1 via mTOR and PI3K signaling, and Foxk1 overexpression promotes adipocyte differentiation while Foxk1 silencing impairs it. ChIP, luciferase reporter assay, Foxk1 overexpression/knockdown in C3H/10T1/2, ST2 and primary BMSCs, nuclear translocation imaging, PI3K/mTOR inhibitor treatment FASEB journal Medium 37889840
2023 FoxK1 directly binds the genome at >4,000 gene promoters/enhancers in hepatocytes; insulin enhances this interaction for ~75% of sites. FoxK1 ChIP-seq binding overlaps with that of the insulin receptor at genes including LARS1 and TIMM22, suggesting FoxK1 acts as a transcriptional partner for some IR-mediated gene regulation. ChIP-seq for FoxK1, IR and FoxO1 in liver cells; siRNA knockdown; gene expression analysis Molecular metabolism Medium 37852413
2025 USP28 interacts with FOXK1 and deubiquitinates it, stabilizing FOXK1 protein. Stabilized FOXK1 activates the Hippo signaling pathway, promoting cell proliferation and radioresistance in lung cancer. In vitro ubiquitination assay, Co-IP, USP28 knockdown, RNA-seq pathway analysis, xenograft model, immunohistochemistry Life sciences Medium 39983825
2025 GARS protein binds to FOXK1 and reduces its ubiquitination, thereby stabilizing FOXK1. Stable FOXK1 then directly transactivates LDHA, PKM2, and GLUT1 promoters to promote glycolysis in hepatocellular carcinoma. Co-IP, ubiquitination assay, ChIP (FOXK1 on glycolytic gene promoters), KLF16 KD/OE, in vitro and in vivo glycolysis assays The Tohoku journal of experimental medicine Medium 40603105
2024 FOXK1 recruits multiple transcriptional corepressor complexes (NCoR/SMRT, SIN3A, NuRD, and REST/CoREST); the FOXK1/NCoR/SIN3A complex transcriptionally represses circadian clock genes including CLOCK, PER2, and CRY2 to promote breast cancer cell proliferation. Insulin resistance elevates OGT, causing nuclear translocation and increased FOXK1 expression. Co-IP (silver staining and mass spectrometry for complex members), ChIP-seq, qChIP, western blot, TUNEL and colony assay, xenograft, FOXK1 OE/KD Cancer letters Medium 39094826
2024 FOXK1 interacts with the REST/CoREST complex (confirmed by Co-IP) to transcriptionally repress apoptotic pathway genes in ER+ breast cancer cells, preventing apoptosis and promoting tumor growth in vivo. Co-IP, ChIP-seq, qChIP, western blot, TUNEL, cell counting and colony assays, xenograft Animal models and experimental medicine Medium 38238876
2024 HDAC1 and FOXK1 interact; the HDAC1-FOXK1 complex silences miR-33a expression, leading to upregulation of ABCB7 and p70S6K1 and conferring EGFR-TKI resistance in non-small cell lung cancer. Co-IP, HDAC1 knockdown/overexpression, miR-33a reporter assay, flow cytometry, Transwell, xenograft Journal of translational medicine Medium 39198847
2023 In renal tubular cells, TGF-β1 induces Foxk1 expression; Foxk1 functions as a transcriptional repressor of the N-cadherin gene. JLP (JNK-associated leucine zipper protein) restrains Foxk1 induction; loss of JLP leads to Foxk1-driven N-cadherin downregulation and a partial EMT state during renal fibrosis. TGF-β1 treatment, Foxk1 overexpression/knockdown, ChIP, luciferase reporter assay (N-cadherin promoter), JLP KO fibrosis model iScience Medium 37013185
2024 KSHV ORF45 binds to FoxK1 and FoxK2 through their FHA domains using a conserved S/T linear motif; ORF45 augments FoxK1/K2 promoter occupancy and transcriptional activity at late viral gene promoters to promote KSHV lytic replication. A single-point mutation in the ORF45 S/T motif abolishes the ORF45-FOXK1/2 interaction. Co-IP, ChIP, luciferase reporter, FHA domain mutagenesis, point mutation of ORF45 S/T motif, FoxK1/K2 siRNA depletion, virion production assay Journal of virology High 39287387 39494902
2016 FOXK1 methylation at its promoter influences FOXK1 gene expression (dual luciferase reporter assay). Paternal age correlates with decreased FOXK1 sperm methylation, and this epigenetic change is transmitted to offspring cord blood on the paternal allele (allele-specific pyrosequencing with informative SNP). Bisulfite pyrosequencing, allele-specific pyrosequencing with informative SNP, dual luciferase reporter assay Human molecular genetics Medium 28171595

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 FOXK1 and FOXK2 regulate aerobic glycolysis. Nature 148 30700909
2020 Aurora-A/SOX8/FOXK1 signaling axis promotes chemoresistance via suppression of cell senescence and induction of glucose metabolism in ovarian cancer organoids and cells. Theranostics 132 32550913
2018 mTORC1 Promotes Metabolic Reprogramming by the Suppression of GSK3-Dependent Foxk1 Phosphorylation. Molecular cell 125 29861159
2018 Circular RNA circMAN2B2 facilitates lung cancer cell proliferation and invasion via miR-1275/FOXK1 axis. Biochemical and biophysical research communications 101 29550475
2020 Long non-coding RNA HUMT hypomethylation promotes lymphangiogenesis and metastasis via activating FOXK1 transcription in triple-negative breast cancer. Journal of hematology & oncology 97 32138762
2017 Noncanonical Pathway for Regulation of CCL2 Expression by an mTORC1-FOXK1 Axis Promotes Recruitment of Tumor-Associated Macrophages. Cell reports 96 29186685
2019 FoxK1 and FoxK2 in insulin regulation of cellular and mitochondrial metabolism. Nature communications 89 30952843
2017 MiR-646 inhibited cell proliferation and EMT-induced metastasis by targeting FOXK1 in gastric cancer. British journal of cancer 84 28632723
2016 Direct regulation of FOXK1 by C-jun promotes proliferation, invasion and metastasis in gastric cancer cells. Cell death & disease 74 27882939
2016 Paternal age effects on sperm FOXK1 and KCNA7 methylation and transmission into the next generation. Human molecular genetics 68 28171595
2002 Absence of p21CIP rescues myogenic progenitor cell proliferative and regenerative capacity in Foxk1 null mice. The Journal of biological chemistry 67 12446708
2007 Sox15 and Fhl3 transcriptionally coactivate Foxk1 and regulate myogenic progenitor cells. The EMBO journal 66 17363903
2022 tRF3008A suppresses the progression and metastasis of colorectal cancer by destabilizing FOXK1 in an AGO-dependent manner. Journal of experimental & clinical cancer research : CR 64 35065674
2012 Foxk1 promotes cell proliferation and represses myogenic differentiation by regulating Foxo4 and Mef2. Journal of cell science 64 22956541
2022 CircSV2b participates in oxidative stress regulation through miR-5107-5p-Foxk1-Akt1 axis in Parkinson's disease. Redox biology 61 35973363
2016 FOXK1 interaction with FHL2 promotes proliferation, invasion and metastasis in colorectal cancer. Oncogenesis 57 27892920
2020 PR-DUB maintains the expression of critical genes through FOXK1/2- and ASXL1/2/3-dependent recruitment to chromatin and H2AK119ub1 deubiquitination. Genome research 54 32747411
2019 ZRANB2/SNHG20/FOXK1 Axis regulates Vasculogenic mimicry formation in glioma. Journal of experimental & clinical cancer research : CR 52 30744670
2018 Coexpression of FOXK1 and vimentin promotes EMT, migration, and invasion in gastric cancer cells. Journal of molecular medicine (Berlin, Germany) 42 30483822
2010 Adenovirus type 5 E1A and E6 proteins of low-risk cutaneous beta-human papillomaviruses suppress cell transformation through interaction with FOXK1/K2 transcription factors. Journal of virology 42 20053746
2019 miR-186-5p Functions as a Tumor Suppressor in Human Osteosarcoma by Targeting FOXK1. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 41 30897321
2012 Sin3 interacts with Foxk1 and regulates myogenic progenitors. Molecular and cellular biochemistry 39 22476904
2018 Knockdown of FOXK1 suppresses liver cancer cell viability by inhibiting glycolysis. Life sciences 38 30312701
2018 Long non-coding RNA LINC01503 promotes colorectal cancer cell proliferation and invasion by regulating miR-4492/FOXK1 signaling. Experimental and therapeutic medicine 38 30542444
2016 Oncogene FOXK1 enhances invasion of colorectal carcinoma by inducing epithelial-mesenchymal transition. Oncotarget 38 27223064
2020 miR-195-5p Suppresses Lung Cancer Cell Proliferation, Migration, and Invasion Via FOXK1. Technology in cancer research & treatment 36 32406336
2019 Long non-coding RNA MCM3AP-AS1 promotes growth and migration through modulating FOXK1 by sponging miR-138-5p in pancreatic cancer. Molecular medicine (Cambridge, Mass.) 36 31830901
2021 SNHG1 knockdown upregulates miR-376a and downregulates FOXK1/Snail axis to prevent tumor growth and metastasis in HCC. Molecular therapy oncolytics 35 34095464
2017 Knockdown of FOXK1 Suppresses Proliferation, Migration, and Invasion in Prostate Cancer Cells. Oncology research 35 28267429
2022 Histone deacetylase 3 contributes to the antiviral innate immunity of macrophages by interacting with FOXK1 to regulate STAT1/2 transcription. Cell reports 33 35081346
2017 FOXK1 plays an oncogenic role in the development of esophageal cancer. Biochemical and biophysical research communications 33 29050933
2010 Fhl2 interacts with Foxk1 and corepresses Foxo4 activity in myogenic progenitors. Stem cells (Dayton, Ohio) 33 20013826
2004 Isolation and developmental expression of Xenopus FoxJ1 and FoxK1. Development genes and evolution 31 14986136
2021 Knockdown of circ‑PVT1 inhibits the progression of lung adenocarcinoma and enhances the sensitivity to cisplatin via the miR‑429/FOXK1 signaling axis. Molecular medicine reports 30 34328193
2020 LncRNA TMPO-AS1 promotes hepatocellular carcinoma cell proliferation, migration and invasion through sponging miR-329-3p to stimulate FOXK1-mediated AKT/mTOR signaling pathway. Cancer medicine 30 32462698
2020 Tumor-derived neomorphic mutations in ASXL1 impairs the BAP1-ASXL1-FOXK1/K2 transcription network. Protein & cell 29 32683582
2017 Knockdown of FOXK1 inhibited the proliferation, migration and invasion in hepatocellular carcinoma cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 28 28551547
2018 LINC02163 regulates growth and epithelial-to-mesenchymal transition phenotype via miR-593-3p/FOXK1 axis in gastric cancer cells. Artificial cells, nanomedicine, and biotechnology 27 29893595
2018 FOXK1 promotes cell growth through activating wnt/β-catenin pathway and emerges as a novel target of miR-137 in glioma. American journal of translational research 27 30018719
2021 circ-PRKCI targets miR-1294 and miR-186-5p by downregulating FOXK1 expression to suppress glycolysis in hepatocellular carcinoma. Molecular medicine reports 26 33880589
2018 Snail/FOXK1/Cyr61 Signaling Axis Regulates the Epithelial-Mesenchymal Transition and Metastasis in Colorectal Cancer. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 26 29794466
2017 RUFY3 interaction with FOXK1 promotes invasion and metastasis in colorectal cancer. Scientific reports 26 28623323
2007 Functional interactions between the Forkhead transcription factor FOXK1 and the MADS-box protein SRF. Nucleic acids research 26 17670796
2017 FOXK1 facilitates cell proliferation through regulating the expression of p21, and promotes metastasis in ovarian cancer. Oncotarget 25 29050292
2020 Circ_0007142/miR-186/FOXK1 axis promoted lung adenocarcinoma progression. American journal of translational research 24 32913545
2019 High FOXK1 expression correlates with poor outcomes in hepatocellular carcinoma and regulates stemness of hepatocellular carcinoma cells. Life sciences 24 31054270
2023 FOXK1 regulates Wnt signalling to promote cardiogenesis. Cardiovascular research 23 37036809
2019 SP1 induced lncRNA CASC11 accelerates the glioma tumorigenesis through targeting FOXK1 via sponging miR-498. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 23 31121483
2004 Identification and characterization of human FOXK1 gene in silico. International journal of molecular medicine 23 15202027
2020 Knockdown of circAPLP2 Inhibits Progression of Colorectal Cancer by Regulating miR-485-5p/FOXK1 Axis. Cancer biotherapy & radiopharmaceuticals 21 32343603
2020 FOXK1 Promotes Proliferation and Metastasis of Gallbladder Cancer by Activating AKT/mTOR Signaling Pathway. Frontiers in oncology 21 32363163
2022 Repression of lncRNA PART1 attenuates ovarian cancer cell viability, migration and invasion through the miR-503-5p/FOXK1 axis. BMC cancer 20 35100978
2018 The FOXK1-CCDC43 Axis Promotes the Invasion and Metastasis of Colorectal Cancer Cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 20 30562730
2022 TRPM2-AS promotes paclitaxel resistance in prostate cancer by regulating FOXK1 via sponging miR-497-5p. Drug development research 19 35238054
2004 Identification and characterization of a novel human FOXK1 gene in silico. International journal of oncology 19 15289879
2020 FOXK1 Participates in DNA Damage Response by Controlling 53BP1 Function. Cell reports 18 32783940
2016 Knockdown of FOXK1 alone or in combination with apoptosis-inducing 5-FU inhibits cell growth in colorectal cancer. Oncology reports 17 27571921
2007 FoxK1 splice variants show developmental stage-specific plasticity of expression with temperature in the tiger pufferfish. The Journal of experimental biology 17 17873000
2025 Foxk1 and Foxk2 promote cardiomyocyte proliferation and heart regeneration. Nature communications 16 40128196
2018 FOXK1 promotes glioblastoma proliferation and metastasis through activation of Snail transcription. Experimental and therapeutic medicine 16 29456714
2022 Recurrent FOXK1::GRHL and GPS2::GRHL fusions in trichogerminoma. The Journal of pathology 15 35049062
2020 Nuclear DLC1 exerts oncogenic function through association with FOXK1 for cooperative activation of MMP9 expression in melanoma. Oncogene 15 32214200
2024 Foxk1 promotes bone formation through inducing aerobic glycolysis. Cell death and differentiation 13 39232134
2020 The lncRNA XIST promotes colorectal cancer cell growth through regulating the miR-497-5p/FOXK1 axis. Cancer cell international 13 33298041
2019 miR-1294 alleviates epithelial-mesenchymal transition by repressing FOXK1 in gastric cancer. Genes & genomics 13 31833046
2023 hucMSCs Treatment Ameliorated Pulmonary Fibrosis via Downregulating the circFOXP1-HuR-EZH2/STAT1/FOXK1 Autophagic Axis. Stem cells (Dayton, Ohio) 11 37419489
2022 Long noncoding RNASEH1-AS1 exacerbates the progression of non-small cell lung cancer by acting as a ceRNA to regulate microRNA-516a-5p/FOXK1 and thereby activating the Wnt/β-catenin signaling pathway. Cancer medicine 11 35166053
2020 LINC00460 Enhances Bladder Carcinoma Cell Proliferation and Migration by Modulating miR-612/FOXK1 Axis. Pharmacology 11 33027786
2019 FOXK1 promotes malignant progression of breast cancer by activating PI3K/AKT/mTOR signaling pathway. European review for medical and pharmacological sciences 11 31799667
2023 miR-144-3p represses hepatocellular carcinoma progression by affecting cell aerobic glycolysis via FOXK1. International journal of experimental pathology 10 36806218
2021 Hsa_circ_0041103 induces proliferation, migration and invasion in bladder cancer via the miR-107/FOXK1 axis. European review for medical and pharmacological sciences 10 33629298
2021 TFAP4 promotes the growth of prostate cancer cells by upregulating FOXK1. Experimental and therapeutic medicine 10 34630654
2022 FoxK1 is Required for Ectodermal Cell Differentiation During Planarian Regeneration. Frontiers in cell and developmental biology 8 35273960
2020 FOXK1 plays an oncogenic role in the progression of hilar cholangiocarcinoma. Molecular medicine reports 8 33300075
2018 Nuclear-cytoplasmic shuttling protein PP2AB56 contributes to mTORC1-dependent dephosphorylation of FOXK1. Genes to cells : devoted to molecular & cellular mechanisms 8 29845697
2023 CangFu Daotan decoction improves polycystic ovarian syndrome by downregulating FOXK1. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 7 37544927
2024 HDAC1 and FOXK1 mediate EGFR-TKI resistance of non-small cell lung cancer through miR-33a silencing. Journal of translational medicine 6 39198847
2023 JLP/Foxk1/N-cadherin axis fosters a partial epithelial-mesenchymal transition state in epithelial tubular cells. iScience 6 37013185
2023 FOXK1 regulates malignant progression and radiosensitivity through direct transcriptional activation of CDC25A and CDK4 in esophageal squamous cell carcinoma. Scientific reports 6 37173384
2023 circPPP2R4 promotes colorectal cancer progression and reduces ROS production through the miR-646/FOXK1 axis. Molecular carcinogenesis 6 37750597
2022 Natural antisense RNA Foxk1-AS promotes myogenic differentiation by inhibiting Foxk1 activity. Cell communication and signaling : CCS 6 35642035
2024 FOXK1 promotes hormonally responsive breast carcinogenesis by suppressing apoptosis. Animal models and experimental medicine 5 38238876
2024 Forkhead box protein FOXK1 disrupts the circadian rhythm to promote breast tumorigenesis in response to insulin resistance. Cancer letters 5 39094826
2021 Mechanisms of miR-195-5p and FOXK1 in rat xenograft models of non-small cell lung cancer. American journal of translational research 5 34017411
2023 FOXK1 regulates epithelial-mesenchymal transition and radiation sensitivity in nasopharyngeal carcinoma via the JAK/STAT3 signaling pathway. Genes & genomics 4 37043129
2023 FOXK1 upregulation is correlated with tumor progression and tumor associated macrophages infiltration in renal cell carcinoma. Molecular carcinogenesis 4 37818826
2021 FOXK1 promotes malignant progression of breast cancer by activating PI3K/AKT/mTOR signaling pathway. European review for medical and pharmacological sciences 4 33755958
2020 Correction to: Long non-coding RNA HUMT hypomethylation promotes lymphangiogenesis and metastasis via activating FOXK1 transcription in triple-negative breast cancer. Journal of hematology & oncology 4 32209117
2019 MicroRNA-652 suppresses malignant phenotypes in glioblastoma multiforme via FOXK1-mediated AKT/mTOR signaling pathway. OncoTargets and therapy 4 31371994
2024 O-GlcNAcylation of FOXK1 orchestrates the E2F pathway and promotes oncogenesis. bioRxiv : the preprint server for biology 3 38463952
2023 FoxK1 associated gene regulatory network in hepatic insulin action and its relationship to FoxO1 and insulin receptor mediated transcriptional regulation. Molecular metabolism 3 37852413
2013 The transcription factor Foxk1 is expressed in developing and adult mouse neuroretina. Gene expression patterns : GEP 3 23714736
2025 USP28-mediated deubiquitination of FOXK1 activates the Hippo signaling pathway to regulate cell proliferation and radiosensitivity in lung cancer. Life sciences 2 39983825
2025 O-GlcNAcylation of FOXK1 co-opts BAP1 to orchestrate the E2F pathway and promotes oncogenesis. Nature communications 2 40593803
2024 Conserved linear motif within the immediate early protein ORF45 promotes its engagement with KSHV lytic cycle-promoting forkhead transcription factors, FOXK1 and FOXK2. Journal of virology 2 39287387
2024 FoxK1 and FoxK2 cooperate with ORF45 to promote late lytic replication of Kaposi's sarcoma-associated herpesvirus. Journal of virology 2 39494902
2023 Foxk1 stimulates adipogenic differentiation via a peroxisome proliferator-activated receptor gamma 2-dependent mechanism. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2 37889840
2025 Circular RNA Circ_0079226 Plays an Oncogenic Role in Gastric Cancer via the miR-155-5p/FOXK1/AKT Pathway. Analytical cellular pathology (Amsterdam) 1 39981141
2025 The LncRNA lnc-POTEM-4:14 promotes HCC progression by interacting with FOXK1. Scientific reports 1 40044876
2025 KLF16-induced Increase of GARS Promotes Glycolysis in Hepatocellular Carcinoma by Stabilizing FOXK1. The Tohoku journal of experimental medicine 1 40603105

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