Affinage

FOXK1

Forkhead box protein K1 · UniProt P85037

Length
733 aa
Mass
75.5 kDa
Annotated
2026-04-28
100 papers in source corpus 42 papers cited in narrative 41 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FOXK1 is a forkhead/winged-helix transcription factor that integrates nutrient and growth factor signaling with transcriptional programs governing aerobic glycolysis, cell cycle progression, differentiation, and DNA repair. Its nuclear-cytoplasmic shuttling is controlled by the mTORC1–GSK3 axis: mTORC1 activation promotes PP2A(B56)-mediated dephosphorylation of FOXK1, enabling nuclear entry and DNA binding, whereas GSK3-dependent phosphorylation triggers 14-3-3 binding and cytoplasmic sequestration (PMID:29861159, PMID:29845697, PMID:30952843). Within the nucleus, FOXK1 functions as a core chromatin-targeting subunit of the PR-DUB complex (BAP1, ASXL1/2, OGT, HCFC1), where O-GlcNAcylation of FOXK1 is required for BAP1 recruitment to E2F target gene regulatory regions to remove H2AK119ub1 and activate transcription (PMID:32747411, PMID:40593803, PMID:32683582). FOXK1 directly binds promoters of glycolytic enzymes (HK2, PFK, PKM, LDHA), pyruvate dehydrogenase kinases, cell cycle regulators (p21, CDC25A, CDK4, CCNB1/CDK1), and lineage-specific genes (Pparγ2, STAT1/2), and recruits corepressor complexes (Sin3, NCoR/SMRT, REST/CoREST) or coactivators in a context-dependent manner to control myogenic progenitor proliferation, cardiomyocyte cell cycle re-entry, osteoblast metabolism, adipogenesis, and antiviral innate immunity (PMID:30700909, PMID:12446708, PMID:40128196, PMID:39232134, PMID:35081346, PMID:37889840, PMID:39094826).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2002 High

    The first genetic loss-of-function study established that Foxk1 is essential for myogenic progenitor cell cycle progression by repressing the CDK inhibitor p21, resolving whether Foxk1 had a functional role beyond DNA binding.

    Evidence Foxk1-null mice and Foxk1/p21 double-knockout epistasis analysis in myogenic progenitor cells

    PMID:12446708

    Open questions at the time
    • Mechanism of p21 repression (direct versus indirect) not established
    • Upstream signals controlling Foxk1 activity unknown
  2. 2007 High

    Identification of SRF as a FOXK1 interaction partner and demonstration that FOXK1 represses SRF target genes established FOXK1 as a transcriptional corepressor that requires partner-factor occupancy for promoter access.

    Evidence Co-immunoprecipitation, ChIP, and luciferase reporter assays on SM α-actin and PPGB promoters

    PMID:17670796

    Open questions at the time
    • Whether SRF-FOXK1 interaction is direct or bridged by other factors
    • Genome-wide scope of SRF-dependent FOXK1 targets unknown
  3. 2010 High

    Discovery that FHL2 cooperates with FOXK1 to repress Foxo4 transcriptional activity linked a LIM-domain cofactor to the FOXK1-mediated control of myogenic progenitor proliferation versus differentiation balance, while viral oncoprotein studies showed that adenovirus E1A and HPV E6 target the FOXK1 FHA domain, indicating evolutionary exploitation of this interaction surface.

    Evidence Yeast two-hybrid and reporter assays for FHL2; TAP-MS, mutagenesis, and transformation assays for E1A/E6

    PMID:20013826 PMID:20053746

    Open questions at the time
    • Structural basis of FOXK1 FHA domain recognition not resolved
    • Physiological relevance of viral–FOXK1 interaction in infection unclear
  4. 2012 Medium

    Mapping of the Sin3 interaction domain to the FOXK1 N-terminus and demonstration that FOXK1 represses both Foxo4 and Mef2 defined the corepressor recruitment mechanism through which FOXK1 maintains myoblast proliferation and blocks premature differentiation.

    Evidence GST pulldown, co-IP, knockdown/overexpression with cell cycle and differentiation readouts in C2C12 myoblasts

    PMID:22476904 PMID:22956541

    Open questions at the time
    • Whether Sin3a and Sin3b are redundant in FOXK1-dependent repression
    • Genome-wide targets of FOXK1–Sin3 not defined
  5. 2017 High

    Phosphoproteomic identification of FOXK1 as an mTORC1-regulated substrate and dissection of the GSK3-dependent phosphorylation/14-3-3 binding/nuclear exclusion circuit revealed how nutrient and growth factor signals control FOXK1 nuclear localization and transcriptional activity.

    Evidence Phosphoproteomics, nuclear fractionation, DNA binding assays, genetic manipulation of mTORC1 and GSK3

    PMID:29186685 PMID:29861159

    Open questions at the time
    • Specific GSK3 phosphorylation sites on FOXK1 not fully mapped
    • Whether mTORC1 acts through additional intermediaries beyond PP2A
  6. 2018 High

    The PP2A regulatory subunit B56 was identified as the specific mediator shuttling the mTORC1 signal to nuclear FOXK1, and insulin-stimulated reciprocal shuttling of FOXK1 (nuclear) versus FoxO1 (cytoplasmic) was demonstrated, establishing the Akt-mTOR-GSK3-PP2A(B56) axis as the complete signaling cascade.

    Evidence Nuclear-cytoplasmic transport inhibition, B56 genetic manipulation, live-cell imaging, RNA-seq in liver cells

    PMID:29845697 PMID:30952843

    Open questions at the time
    • Whether additional phosphatases contribute in specific tissues
    • Quantitative kinetics of FOXK1 shuttling not established
  7. 2019 High

    A landmark metabolic study demonstrated that FOXK1 directly activates transcription of glycolytic enzymes (HK2, PFK, PKM2, LDHA) and pyruvate dehydrogenase kinases while repressing pyruvate dehydrogenase phosphatase, establishing FOXK1 as a master transcriptional driver of aerobic glycolysis (Warburg effect).

    Evidence Transcriptional assays, in vivo mouse models, primary human cell studies with comprehensive metabolic and gene expression analysis

    PMID:30700909

    Open questions at the time
    • Whether FOXK1 and FOXK2 are fully redundant in glycolytic gene activation
    • Direct versus indirect targets not genome-wide resolved at this stage
  8. 2020 High

    FOXK1 was established as a core chromatin-targeting subunit of the PR-DUB complex (BAP1/ASXL1/HCFC1/OGT) required for genome-wide BAP1 recruitment, H2AK119ub1 removal, and gene activation, while leukemia-associated ASXL1 truncation mutations were shown to disrupt the ASXL1–FOXK1 interaction and target gene expression.

    Evidence ChIP-seq, CRISPR knockout, mass spectrometry, allele-specific deletion, transcriptomic analysis

    PMID:32683582 PMID:32747411

    Open questions at the time
    • Whether FOXK1 and FOXK2 share all PR-DUB target sites
    • How FOXK1 is itself recruited to specific genomic loci
  9. 2020 High

    Discovery that FOXK1 interacts with 53BP1 in an ATM/CHK2-dependent manner during S phase and shifts DNA repair from NHEJ toward HR by displacing RIF1/PTIP extended FOXK1 function beyond transcription into DNA damage response regulation.

    Evidence Co-IP, live-cell imaging, siRNA, PARPi sensitivity and telomere fusion assays

    PMID:32783940

    Open questions at the time
    • Structural basis of FOXK1–53BP1 interaction unresolved
    • Whether this function is FHA-domain dependent
    • Relevance in non-cancer primary cells not tested
  10. 2022 High

    HDAC3 was shown to protect FOXK1 from lysosomal degradation and co-occupy STAT1/STAT2 promoters with FOXK1, establishing a FOXK1-dependent transcriptional mechanism for innate antiviral immunity in macrophages.

    Evidence Co-IP, ChIP, CRISPR KO macrophages, viral challenge assays

    PMID:35081346

    Open questions at the time
    • Mechanism of HDAC3-mediated protection from lysosomal degradation unknown
    • Whether FOXK1 acts as activator or derepressor at STAT1/2 loci
  11. 2023 High

    FOXK1 was shown to repress Wnt/β-catenin signaling during cardiogenesis and to directly activate cardiac cell cycle genes CCNB1/CDK1, establishing its role as a key regulator of cardiac progenitor differentiation and cardiomyocyte proliferation.

    Evidence CRISPR KO embryoid bodies, ATAC-seq, RNA-seq, cardiomyocyte-specific KO, AAV9 rescue, in vivo MI model

    PMID:37036809 PMID:40128196

    Open questions at the time
    • Whether FOXK1 directly binds Wnt pathway gene promoters
    • Redundancy with FOXK2 in cardiomyocytes not addressed
  12. 2024 High

    CUT&Tag and conditional KO in osteoblasts confirmed that FOXK1 directly occupies glycolytic gene promoters in bone, and that its metabolic function is required for bone formation, generalizing the FOXK1–glycolysis axis to mesenchymal lineages.

    Evidence CUT&Tag, conditional Foxk1 KO in preosteoblasts, glycolysis assays, bone microstructure analysis, AAV rescue with glycolysis inhibitor

    PMID:39232134

    Open questions at the time
    • Whether HIF1α mediates FOXK1's glycolytic effects in bone as in heart
    • Contribution of FOXK2 in osteoblasts untested
  13. 2024 High

    KSHV ORF45 was found to bind the FOXK1 FHA domain through a phosphothreonine-containing linear motif, augmenting FOXK1 promoter binding and late viral gene transcription — revealing that viruses exploit FOXK1's FHA domain to hijack host transcriptional machinery.

    Evidence Co-IP, point mutagenesis of ORF45 threonine, ChIP, lytic reactivation assays

    PMID:39287387 PMID:39494902

    Open questions at the time
    • Whether cellular FHA-binding partners use the same motif
    • Crystal structure of FOXK1 FHA–ligand complex not available
  14. 2025 High

    O-GlcNAcylation of FOXK1 was shown to be required for BAP1 recruitment to E2F target gene regulatory regions and for maintaining active chromatin; this modification is cell-cycle regulated, peaking at G1/S, and is essential for FOXK1-driven cellular transformation.

    Evidence O-GlcNAc site mutagenesis, ChIP-seq, chromatin modification analysis, proliferation/transformation assays, tumor growth assays

    PMID:40593803

    Open questions at the time
    • Identity and number of specific O-GlcNAcylated residues governing BAP1 interaction not fully mapped
    • Whether O-GlcNAcylation affects FOXK1 interactions beyond BAP1
  15. 2025 Medium

    USP28-mediated deubiquitination was identified as a mechanism stabilizing FOXK1 protein levels, adding another layer of post-translational regulation distinct from HDAC3-mediated lysosomal protection.

    Evidence In vitro ubiquitination assay, co-IP, RNA-seq, xenograft model

    PMID:39983825

    Open questions at the time
    • E3 ligase responsible for FOXK1 ubiquitination not identified
    • Relationship between USP28 and HDAC3 protective mechanisms unclear
    • Single-lab finding awaits independent confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: (1) the structural basis for FOXK1's context-dependent switching between transcriptional activation and repression; (2) the full catalog of O-GlcNAcylation sites and how each modifies specific protein interactions; (3) whether FOXK1 and FOXK2 are truly redundant at most genomic loci; and (4) how FOXK1's transcriptional, chromatin-remodeling, and DNA repair functions are coordinated in a cell-cycle-dependent manner.
  • No high-resolution structural model of FOXK1 in complex with chromatin or cofactors
  • Genome-wide functional separation of FOXK1 vs FOXK2 not systematically performed
  • Integration of metabolic, cell cycle, and DNA repair functions into a unified regulatory model lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 11 GO:0003677 DNA binding 10
Localization
GO:0005634 nucleus 6 GO:0005829 cytosol 2
Pathway
R-HSA-74160 Gene expression (Transcription) 11 R-HSA-1640170 Cell Cycle 6 R-HSA-162582 Signal Transduction 5 R-HSA-1266738 Developmental Biology 4 R-HSA-1430728 Metabolism 4 R-HSA-4839726 Chromatin organization 3 R-HSA-168256 Immune System 1 R-HSA-73894 DNA Repair 1
Partners
ASXL1BAP1FHL2HDAC3OGTSIN3ASRFTP53BP1
Complex memberships
NCoR/SMRT corepressor complexPR-DUB (BAP1/ASXL1/HCFC1/OGT)REST/CoREST corepressor complexSIN3 corepressor complex

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2019 FOXK1 and FOXK2 induce aerobic glycolysis by transcriptionally upregulating glycolytic enzymes (hexokinase-2, phosphofructokinase, pyruvate kinase, lactate dehydrogenase) and suppressing mitochondrial pyruvate oxidation by increasing pyruvate dehydrogenase kinases 1 and 4 and suppressing pyruvate dehydrogenase phosphatase 1, leading to increased phosphorylation of the E1α subunit of the pyruvate dehydrogenase complex and thus diverting pyruvate to lactate. In vitro transcriptional assays, in vivo mouse models, primary human cell studies, gene expression analysis Nature High 30700909
2018 mTORC1 promotes nuclear localization and activity of FOXK1 by suppressing GSK3-dependent phosphorylation of FOXK1; when mTORC1 is suppressed, GSK3 phosphorylates FOXK1, inducing 14-3-3 binding, reduced DNA binding, and nuclear exclusion. This pathway regulates glycolytic and anabolic gene expression including HIF-1α. Phosphoproteomics, co-immunoprecipitation, nuclear fractionation, DNA binding assays, genetic manipulation of mTORC1/GSK3 Molecular cell High 29861159
2019 Following insulin stimulation, FOXK1 and FOXK2 translocate from cytoplasm to nucleus in a reciprocal manner to FoxO1; this translocation is dependent on the Akt-mTOR pathway, while cytoplasmic localization in basal state is dependent on GSK3. Knockdown of FoxK1/K2 in liver cells upregulates apoptosis genes and downregulates cell cycle and lipid metabolism genes, leading to decreased proliferation and altered mitochondrial fatty acid metabolism. Subcellular fractionation, live cell imaging, siRNA knockdown, RNA-seq, pathway inhibitor experiments Nature communications High 30952843
2017 mTORC1 activation induces PP2A-mediated dephosphorylation of FOXK1, resulting in transactivation of the CCL2 gene in a manner independent of NF-κB; this promotes tumor-associated macrophage recruitment. Identified by phosphoproteomics as a downstream target of mTORC1. Multiple phosphoproteomics approaches, luciferase reporter assay, chromatin immunoprecipitation, in vivo tumor models Cell reports High 29186685
2002 Foxk1 is essential for myogenic progenitor cell cycle progression; Foxk1-null mice show G0/G1 arrest and upregulation of the CDK inhibitor p21CIP. Combinatorial knockout of Foxk1 and p21CIP rescues growth deficit, muscle regeneration, and cell cycle progression, placing p21CIP downstream of Foxk1. Genetic epistasis (double-mutant mice), cell cycle analysis, molecular analysis of Foxk1-/- myogenic progenitor cells The Journal of biological chemistry High 12446708
2012 FOXK1 promotes myogenic progenitor cell proliferation and represses differentiation by physically interacting with and repressing the transcriptional activity of Foxo4 and Mef2. Knockdown of Foxk1 in C2C12 myoblasts causes cell cycle arrest, and overexpression retards muscle differentiation. Co-immunoprecipitation, transcriptional reporter assays, knockdown and overexpression experiments, cell cycle analysis Journal of cell science High 22956541
2007 FOXK1 interacts with SRF in human cells and acts as a transcriptional repressor of SRF target genes SM alpha-actin and PPGB; FOXK1 binding to these promoters requires SRF occupancy. Co-immunoprecipitation, chromatin immunoprecipitation, luciferase reporter assay, promoter binding studies Nucleic acids research High 17670796
2010 FOXK1 interacts with the LIM-only protein Fhl2; Fhl2 dose-dependently promotes FOXK1-mediated transcriptional repression of Foxo4 activity in myogenic progenitor cells. Fhl2 knockdown causes cell cycle arrest and mice lacking Fhl2 show perturbed skeletal muscle regeneration. Yeast two-hybrid screen, transcriptional reporter assays, knockdown experiments, in vivo mouse regeneration model Stem cells Medium 20013826
2012 Foxk1 interacts with Sin3 transcriptional corepressor through the Foxk1 N-terminal (1-40) region (Sin3 interacting domain) and the PAH2 domain of Sin3, as determined by yeast two-hybrid and GST pulldown. Sin3a/b knockdown results in cell cycle arrest and upregulation of cell cycle inhibitor genes in myogenic progenitor cells. Yeast two-hybrid screen, GST pulldown assay, siRNA knockdown, cell cycle analysis Molecular and cellular biochemistry Medium 22476904
2007 Sox15 directly binds an evolutionarily conserved site in the Foxk1 promoter and recruits Fhl3 to transcriptionally coactivate Foxk1 gene expression in myogenic progenitor cells. Sox15 knockdown reduces Foxk1 expression and perturbs cell cycle kinetics; Sox15 mutant mice show perturbed skeletal muscle regeneration. Transgenic reporter assay, chromatin immunoprecipitation, knockdown experiments, Sox15 mutant mouse analysis The EMBO journal High 17363903
2010 Adenovirus E1A C-terminus and beta-HPV E6 proteins interact with FOXK1/K2 through a conserved Ser/Thr-containing motif; E1A mutants deficient in FOXK1/K2 interaction show enhanced cell proliferation and oncogenic transformation, demonstrating that FOXK1/K2 interaction suppresses E1A-mediated transformation. Tandem affinity purification, mass spectrometry, co-immunoprecipitation, cell transformation assays, mutational analysis Journal of virology High 20053746
2020 FOXK1 is a core component of the PR-DUB complex (with BAP1, HCFC1, OGT, and ASXL proteins) and is required for BAP1-mediated H2AK119ub1 deubiquitination and recruitment to chromatin for gene activation. FOXK1/2 facilitate BAP1 genome-wide binding and gene activation independently of PRC2. ChIP-seq, CRISPR knockout, mass spectrometry complex analysis, genome-wide transcriptomic analysis Genome research High 32747411
2020 ASXL1 interacts with FOXK1 and FOXK2 to regulate a subset of FOXK1/K2 target genes; C-terminally truncated mutant ASXL1 (leukemia-associated) loses the ability to interact with FOXK1/K2, and specific deletion of the mutant allele restores BAP1-ASXL1-FOXK1/K2 target gene expression involved in glucose metabolism, oxygen sensing, and JAK-STAT3 signaling. Co-immunoprecipitation, mass spectrometry, allele-specific deletion, gene expression analysis Protein & cell High 32683582
2020 FOXK1 associates with 53BP1 and regulates 53BP1-dependent DNA repair choice between NHEJ and HR. The FOXK1-53BP1 interaction is enhanced upon DNA damage during S phase in an ATM/CHK2-dependent manner, reducing 53BP1 association with RIF1 and PTIP. FOXK1 overexpression diminishes 53BP1 foci and leads to resistance to PARPi in BRCA1-deficient cells. Co-immunoprecipitation, live cell imaging, siRNA depletion, PARPi sensitivity assays, telomere fusion assays, DNA damage response analysis Cell reports High 32783940
2022 HDAC3 interacts with FOXK1 and co-localizes with it at the promoters of STAT1 and STAT2; HDAC3 is required to protect FOXK1 from lysosomal system-mediated degradation. Loss of either HDAC3 or FOXK1 in macrophages decreases STAT1/STAT2 expression and impairs antiviral immunity. Co-immunoprecipitation, chromatin immunoprecipitation, CRISPR knockout, gene expression analysis, viral challenge assays Cell reports High 35081346
2016 FOXK1 physically interacts with FHL2 in colorectal cancer cells; siRNA-mediated repression of FHL2 in FOXK1-overexpressing cells reverses EMT, proliferative, and metastatic phenotypes in vitro and in vivo. Co-immunoprecipitation, shRNA-mediated knockdown, in vitro migration/invasion assays, in vivo xenograft Oncogenesis Medium 27892920
2018 FOXK1 physically interacts with and stabilizes vimentin in gastric cancer cells; co-expression of FOXK1 and vimentin enhances EMT, and siRNA repression of vimentin in FOXK1-overexpressing cells reverses the EMT-like phenotype. Co-immunoprecipitation, siRNA knockdown, in vitro EMT assays, in vivo xenograft Journal of molecular medicine Medium 30483822
2016 c-jun directly binds to and activates the human FOXK1 gene promoter, as demonstrated by promoter reporter and chromatin immunoprecipitation assays. siRNA-mediated repression of c-jun in FOXK1-overexpressing cells reverses EMT and proliferative/metastatic phenotypes. Luciferase reporter assay, chromatin immunoprecipitation, siRNA knockdown, in vivo orthotopic implantation Cell death & disease Medium 27882939
2018 Snail directly binds to and activates the human FOXK1 gene promoter; FOXK1 in turn directly activates transcription of Cyr61 (confirmed by luciferase assays), mediating Snail/FOXK1/Cyr61-driven EMT and metastasis in colorectal cancer. Chromatin immunoprecipitation, luciferase reporter assay, in vitro migration/invasion assays, in vivo metastasis model Cellular physiology and biochemistry Medium 29794466
2018 FOXK1 directly binds and activates the human CCDC43 gene promoter (confirmed by chromatin immunoprecipitation and promoter assays), and CCDC43 is required for FOXK1-mediated EMT and metastasis in colorectal cancer. Chromatin immunoprecipitation, luciferase reporter assay, siRNA knockdown, flow cytometry, invasion assays Cellular physiology and biochemistry Medium 30562730
2017 FOXK1 physically interacts with RUFY3 in colorectal cancer cells; siRNA-mediated repression of FOXK1 in RUFY3-overexpressing cells reverses EMT and metastatic phenotypes in vitro and in vivo. Co-immunoprecipitation, immunofluorescence, siRNA knockdown, in vivo orthotopic implantation Scientific reports Medium 28623323
2018 FOXK1 promotes glioblastoma cell proliferation via the S-phase and activates transcription of Snail, as demonstrated by luciferase reporter assay and chromatin immunoprecipitation, thereby promoting EMT and metastasis. Luciferase reporter assay, chromatin immunoprecipitation, loss/gain of function experiments Experimental and therapeutic medicine Medium 29456714
2017 FOXK1 facilitates cell cycle progression in ovarian cancer by transcriptionally regulating p21 expression, as shown by ChIP and luciferase reporter assay. FOXK1 knockdown leads to reduced proliferation and cell cycle arrest. Chromatin immunoprecipitation, luciferase reporter assay, cell cycle analysis, CCK-8 and colony formation assays Oncotarget Medium 29050292
2018 FOXK1 suppression in liver cancer cells reduces hexokinase 2 (HK2) expression, decreases glucose consumption and lactate production, and inhibits the Akt/mTOR pathway, demonstrating that FOXK1 promotes aerobic glycolysis through HK2 and Akt/mTOR. siRNA knockdown, qRT-PCR, western blot, glucose consumption and lactate production assays, MTT/CCK-8 Life sciences Medium 30312701
2020 FOXK1 interacts with the transcription factor DLC1 in the nucleus of melanoma cells (identified by mass spectrometry); DLC1-FOXK1 cooperatively activates MMP9 expression through FOXK1-mediated promoter occupancy, promoting invasion and metastasis independent of DLC1's RhoGAP activity. Mass spectrometry, co-immunoprecipitation, chromatin immunoprecipitation, RNA-sequencing, loss/gain of function assays Oncogene High 32214200
2018 Nuclear-cytoplasmic shuttling of PP2A regulatory subunit B56 is required for mTORC1-dependent dephosphorylation of FOXK1; B56 acts as the mediating component between cytoplasmic mTORC1 and nuclear FOXK1. Nuclear-cytoplasmic transport inhibition, phosphorylation assays, genetic manipulation of B56 Genes to cells Medium 29845697
2023 FOXK1 regulates cardiogenesis by repressing the Wnt/β-catenin signaling pathway to promote cardiac progenitor cell differentiation; Foxk1 KO embryoid bodies show impaired chromatin accessibility at cardiac regulatory regions and reduced expression of the cardiac molecular program. CRISPR KO, flow cytometry, bulk RNA-seq, ATAC-seq, ChIP-qPCR, cardiac beating and contractility assays Cardiovascular research High 37036809
2025 Foxk1 and Foxk2 drive cardiomyocyte cell cycle progression by directly activating CCNB1 and CDK1 expression, forming the CCNB1/CDK1 complex that facilitates G2/M transition. They also promote cardiomyocyte proliferation by upregulating HIF1α, which enhances glycolysis and the pentose phosphate pathway. Cardiomyocyte-specific KO, AAV9-mediated overexpression, ChIP, RNA-seq, in vivo myocardial infarction model Nature communications High 40128196
2024 FOXK1 binds to promoter regions of glycolytic enzyme genes (identified by CUT&Tag analysis) and promotes aerobic glycolysis in osteoblasts; conditional KO of Foxk1 in preosteoblasts reduces aerobic glycolysis and decreases bone mass and mechanical strength, an effect rescued by Foxk1 overexpression but blocked by glycolysis inhibition. CUT&Tag, conditional KO mouse model, glycolysis assays, bone microstructure analysis, AAV-mediated overexpression Cell death and differentiation High 39232134
2020 Aurora-A kinase phosphorylates the transcription factor SOX8 at Ser327, which in turn promotes FOXK1 expression, thereby regulating genes related to cell senescence (hTERT, P16) and glycolysis (LDHA, HK2) to drive chemoresistance in ovarian cancer. Immunoprecipitation, mass spectrometry, FRET-FLIM, luciferase reporter assay, ChIP, organoid models Theranostics High 32550913
2023 FOXK1 directly binds to promoter regions of CDC25A and CDK4 and activates their transcription in esophageal squamous cell carcinoma cells (confirmed by ChIP and luciferase assay); knockdown of either CDC25A or CDK4 reverses FOXK1 overexpression-mediated biological effects including radioresistance. Chromatin immunoprecipitation, luciferase reporter assay, siRNA knockdown, radiation sensitivity assays, cell cycle analysis Scientific reports Medium 37173384
2025 FOXK1, but not FOXK2, is specifically modified by O-GlcNAcylation; this modification is modulated during the cell cycle and peaks at G1/S. O-GlcNAcylation of FOXK1 is required for its ability to recruit BAP1 to E2F target gene regulatory regions, maintain active chromatin (reduced H2AK119ub, maintained H3K4me1), and promote E2F pathway gene expression, cell proliferation, and cellular transformation. O-GlcNAc mutagenesis, ChIP-seq, cell proliferation/transformation assays, chromatin modification analysis, tumor growth assays Nature communications High 40593803
2024 FOXK1 O-GlcNAcylation is identified; FOXK1 O-GlcNAc-defective mutants show reduced BAP1 recruitment to E2F target genes and increased H2AK119ub levels, confirming that O-GlcNAcylation co-opts the tumor suppressor BAP1 to promote transcription of E2F target genes and oncogenesis. O-GlcNAc mutagenesis, ChIP-seq, gene expression analysis, tumor growth assays bioRxivpreprint High 38463952
2024 FOXK1 recruits the REST/CoREST transcriptional corepression complex to transcriptionally inhibit apoptotic pathway genes in ER+ breast cancer cells, as determined by ChIP-seq and mass spectrometry; this prevents apoptosis and promotes ER+ breast tumor progression. Silver staining mass spectrometry, Co-IP, ChIP-seq, TUNEL assay, xenograft models Animal models and experimental medicine Medium 38238876
2024 FOXK1 recruits multiple corepressor complexes (NCoR/SMRT, SIN3A, NuRD, REST/CoREST); the FOXK1/NCoR/SIN3A complex transcriptionally represses circadian clock genes CLOCK, PER2, and CRY2, promoting breast cancer proliferation. Insulin resistance increases OGT expression, which causes FOXK1 nuclear translocation and increased expression. ChIP-seq, co-immunoprecipitation, luciferase reporter assay, chromatin modification analysis, inhibitor studies Cancer letters Medium 39094826
2023 FoxK1 binding sites are found at promoters and enhancers of over 4000 genes in liver cells; insulin enhances FoxK1 binding at ~75% of target genes. ChIP-seq comparison shows that FoxK1 may act as a transcription factor partner for some reported roles of the insulin receptor in gene regulation. ChIP-seq, siRNA knockdown, gene expression analysis Molecular metabolism Medium 37852413
2025 USP28 interacts with FOXK1 and mediates its deubiquitination and stabilization; FOXK1 promotes cell proliferation and radioresistance in lung cancer through activation of the Hippo signaling pathway. In vitro ubiquitination assay, co-immunoprecipitation, RNA-seq, xenograft model, siRNA knockdown Life sciences Medium 39983825
2024 KSHV ORF45 binds FOXK1 via a conserved serine/threonine linear motif that interacts with the FOXK1 FHA domain; a single threonine point mutation in ORF45 abolishes this interaction. FoxK1 and FoxK2 directly bind to promoters of several late viral genes, and ORF45 augments their promoter binding and transcriptional activity to promote late viral gene expression. Co-immunoprecipitation, mutagenesis, ChIP, lytic reactivation assays, depletion experiments Journal of virology High 39287387 39494902
2023 Foxk1 directly binds to the Pparγ2 promoter and stimulates its transcriptional activity, promoting adipocyte differentiation from progenitor cells. Adipogenic stimulation induces nuclear translocation of Foxk1 in an mTOR- and PI3-kinase-dependent manner. ChIP, luciferase reporter assay, loss/gain of function in BMSCs and cell lines, pathway inhibitor studies FASEB journal Medium 37889840
2022 A natural antisense RNA, Foxk1-AS, is transcribed from the opposite strand of Foxk1 DNA and targets Foxk1 to suppress its expression; overexpression of Foxk1-AS inhibits Foxk1 and promotes myoblast differentiation and muscle regeneration by rescuing Mef2c activity. Lentivirus/AAV overexpression and knockdown, qRT-PCR, western blotting, immunofluorescence, in vivo muscle regeneration model Cell communication and signaling Medium 35642035
2025 O-GlcNAcylation of FOXK1 at Thr573 (identified by proteomic profiling) inhibits ubiquitination-mediated degradation of PES1; increased PES1 promotes AKR1C18 activity to reduce progesterone levels, thereby disrupting oocyte maturation and early embryonic development. Proteomic O-GlcNAcylation profiling, co-immunoprecipitation combined with LC-MS/MS, site-specific mutagenesis, in vivo mouse exposure model Advanced science Medium 41388345

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 147 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 129 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 95 32138762
2017 Noncanonical Pathway for Regulation of CCL2 Expression by an mTORC1-FOXK1 Axis Promotes Recruitment of Tumor-Associated Macrophages. Cell reports 94 29186685
2019 FoxK1 and FoxK2 in insulin regulation of cellular and mitochondrial metabolism. Nature communications 87 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 67 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
2012 Foxk1 promotes cell proliferation and represses myogenic differentiation by regulating Foxo4 and Mef2. Journal of cell science 64 22956541
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 63 35065674
2022 CircSV2b participates in oxidative stress regulation through miR-5107-5p-Foxk1-Akt1 axis in Parkinson's disease. Redox biology 60 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 53 32747411
2019 ZRANB2/SNHG20/FOXK1 Axis regulates Vasculogenic mimicry formation in glioma. Journal of experimental & clinical cancer research : CR 51 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 41 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 40 30897321
2012 Sin3 interacts with Foxk1 and regulates myogenic progenitors. Molecular and cellular biochemistry 39 22476904
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
2018 Knockdown of FOXK1 suppresses liver cancer cell viability by inhibiting glycolysis. Life sciences 37 30312701
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
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
2022 Histone deacetylase 3 contributes to the antiviral innate immunity of macrophages by interacting with FOXK1 to regulate STAT1/2 transcription. Cell reports 31 35081346
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 29 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 29 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
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
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 25 29794466
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
2004 Identification and characterization of human FOXK1 gene in silico. International journal of molecular medicine 23 15202027
2019 SP1 induced lncRNA CASC11 accelerates the glioma tumorigenesis through targeting FOXK1 via sponging miR-498. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 22 31121483
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
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
2025 Foxk1 and Foxk2 promote cardiomyocyte proliferation and heart regeneration. Nature communications 14 40128196
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
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 CangFu Daotan decoction improves polycystic ovarian syndrome by downregulating FOXK1. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 6 37544927
2023 circPPP2R4 promotes colorectal cancer progression and reduces ROS production through the miR-646/FOXK1 axis. Molecular carcinogenesis 6 37750597
2024 FOXK1 promotes hormonally responsive breast carcinogenesis by suppressing apoptosis. Animal models and experimental medicine 5 38238876
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
2024 Forkhead box protein FOXK1 disrupts the circadian rhythm to promote breast tumorigenesis in response to insulin resistance. Cancer letters 4 39094826
2023 FOXK1 upregulation is correlated with tumor progression and tumor associated macrophages infiltration in renal cell carcinoma. Molecular carcinogenesis 4 37818826
2022 Natural antisense RNA Foxk1-AS promotes myogenic differentiation by inhibiting Foxk1 activity. Cell communication and signaling : CCS 4 35642035
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 regulates epithelial-mesenchymal transition and radiation sensitivity in nasopharyngeal carcinoma via the JAK/STAT3 signaling pathway. Genes & genomics 3 37043129
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
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 O-GlcNAcylation of FOXK1 co-opts BAP1 to orchestrate the E2F pathway and promotes oncogenesis. Nature communications 1 40593803
2025 PFOS Disrupts Oocyte Maturation and Early Embryonic Development via Ovarian FOXK1 O-GlcNAcylation in Mice. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41388345