Affinage

FOXK2

Forkhead box protein K2 · UniProt Q01167

Length
660 aa
Mass
69.1 kDa
Annotated
2026-04-28
56 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FOXK2 is a forkhead-box transcription factor that integrates signal-dependent nuclear-cytoplasmic shuttling with chromatin remodeling to control cell proliferation, metabolic reprogramming, and differentiation. Its FHA domain recruits the BAP1 deubiquitinase complex (via phospho-Thr493 on BAP1) and multiple corepressor complexes (SIN3A, NCoR/SMRT, NuRD, REST/CoREST) to repress target genes including HIF1β and EZH2, while it also functions as a transcriptional activator of glycolytic enzymes, CCNB1/CDK1, PPARγ, IRE1α, and VEGFA through direct promoter or enhancer binding (PMID:25451922, PMID:27773593, PMID:30700909, PMID:35349489, PMID:40128196, PMID:39789420). Nuclear entry and transcriptional output are controlled by insulin/Akt–mTOR signaling (promoting nuclear translocation opposed by GSK3-mediated cytoplasmic retention), PIAS4-mediated SUMOylation at K527/K633, CBP acetylation at K223 counteracted by SIRT1 deacetylation, CDK1/2 phosphorylation at S368/S423 during mitosis, PDK2 phosphorylation at T13/S30, and FBXO24-mediated polyubiquitylation leading to proteasomal degradation (PMID:30952843, PMID:36682222, PMID:34866322, PMID:20810654, PMID:38734828, PMID:38735474). Loss-of-function mutations in FOXK2 cause congenital myopathy with ptosis, linked to impaired myogenic differentiation and disrupted mitochondrial homeostasis in muscle stem cells (PMID:40410591).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1992 Medium

    Identification of FOXK2 as a forkhead-domain transcription factor established that it uses this domain for sequence-specific DNA binding to purine-rich regulatory elements, providing the first molecular handle on the gene.

    Evidence EMSA and expression library screening with HIV-1 LTR and IL-2 promoter probes

    PMID:1339390

    Open questions at the time
    • Endogenous genomic targets unknown
    • No functional consequence of DNA binding demonstrated
    • In vitro binding only, no chromatin context
  2. 2010 High

    Demonstration that CDK1/cyclin B and CDK2/cyclin A phosphorylate FOXK2 at S368 and S423 during mitosis revealed the first regulatory post-translational modification controlling its stability and repressor activity, and showed that disrupting this regulation triggers apoptosis.

    Evidence In vitro kinase assays, site-directed mutagenesis, cell cycle synchronization, transcriptional reporters

    PMID:20810654

    Open questions at the time
    • Phosphatase(s) reversing these modifications unidentified
    • Downstream apoptotic pathway not fully dissected
    • In vivo relevance not tested
  3. 2010 Medium

    Discovery that FOXK2's forkhead domain binds G/T-mismatch DNA with higher affinity than matched consensus raised the possibility of a non-canonical role in DNA damage recognition, though functional consequences remain unclear.

    Evidence EMSA with recombinant forkhead domain and antibody supershift in HL60 nuclear extracts

    PMID:20097901

    Open questions at the time
    • No demonstration of mismatch repair activity
    • Physiological relevance of mismatch binding untested
    • Single-lab finding without in vivo validation
  4. 2011 High

    Genome-wide ChIP-seq showed FOXK2 binding sites are enriched for AP-1 motifs and that FOXK2 is required for efficient AP-1 chromatin recruitment, establishing FOXK2 as a pioneer or cooperative factor for AP-1-dependent transcription.

    Evidence ChIP-seq, ChIP-qPCR, knockdown with gene expression analysis

    PMID:22083952

    Open questions at the time
    • Mechanism of cooperative binding (direct interaction vs. chromatin remodeling) not resolved
    • AP-1 subunit specificity not defined
  5. 2014 High

    Biochemical dissection of the FOXK2–BAP1 axis showed that the FHA domain of FOXK2 recognizes phospho-Thr493 on BAP1 to recruit the PR-DUB complex to chromatin, where BAP1's deubiquitinase activity on H2AK119ub is required for target gene repression — establishing FOXK2 as a sequence-specific recruiter of an epigenetic eraser.

    Evidence Co-IP, pulldown, domain mapping, histone deubiquitination assays, ChIP, RNAi epistasis with Ring1B–Bmi1

    PMID:24748658 PMID:25451922

    Open questions at the time
    • Kinase phosphorylating BAP1 T493 to enable FOXK2 interaction not identified in these studies
    • Structural basis of FHA–pThr recognition not resolved
    • Genome-wide extent of FOXK2-dependent H2A deubiquitination not mapped
  6. 2015 High

    FOXK2 was shown to scaffold the BRCA1/BARD1 E3 ligase onto ERα, promoting ERα ubiquitylation and degradation, revealing a non-transcriptional adaptor function in protein turnover that links FOXK2 to estrogen signaling and breast cancer cell proliferation.

    Evidence Co-IP, ubiquitination assays, reporter assays, double knockdown epistasis

    PMID:25740706

    Open questions at the time
    • Whether FOXK2 scaffolding of BRCA1/BARD1 extends to other substrates unknown
    • Structural basis of tripartite complex not resolved
  7. 2016 High

    Identification of FOXK2 interactions with four distinct corepressor complexes (NCoR/SMRT, SIN3A, NuRD, REST/CoREST) and its repression of HIF1β and EZH2 positioned FOXK2 as a multi-complex transcriptional repressor that suppresses the hypoxic response.

    Evidence Co-IP with multiple complexes, ChIP, knockdown/overexpression, luciferase reporters

    PMID:27773593

    Open questions at the time
    • How FOXK2 selects among different corepressor complexes at specific loci unknown
    • Stoichiometry of complex engagement at individual promoters not determined
  8. 2018 High

    Mapping SUMOylation at K527 and K633 and showing that these modifications are required for FOXK2 binding to the FOXO3 promoter and for paclitaxel sensitivity established SUMOylation as a critical activating switch for FOXK2's transcriptional function.

    Evidence SUMO-site mutagenesis, ChIP, clonogenic and viability assays

    PMID:29540677

    Open questions at the time
    • SUMO E3 ligase responsible not identified in this study (later found to be PIAS4)
    • Mechanism by which SUMO modification enables DNA binding unclear
  9. 2019 High

    Two landmark studies established FOXK2 (with FOXK1) as a master metabolic switch: it transcriptionally upregulates glycolytic enzymes and PDK1/4 while suppressing PDP1 to drive aerobic glycolysis, and its nuclear translocation is controlled by the insulin–Akt–mTOR axis opposed by GSK3 cytoplasmic retention — linking growth factor signaling to metabolic gene programs.

    Evidence KO/KD/OE in multiple cell types and in vivo mice, metabolic flux assays, subcellular fractionation, pharmacological inhibitors, RNA-seq

    PMID:30700909 PMID:30952843

    Open questions at the time
    • Direct phosphorylation sites mediating Akt/mTOR-dependent nuclear import not mapped
    • Relative contributions of FOXK1 vs FOXK2 to glycolytic regulation not fully separated
  10. 2021 High

    Multiple 2021 studies expanded FOXK2's transcriptional target repertoire to include IRE1α (via intronic enhancer binding driving UPR/stemness), VEGFA (driving angiogenesis with a VEGFR1-mediated feedback loop), and identified CBP-mediated K223 acetylation counteracted by SIRT1 as a regulatory switch controlling nuclear localization and chemosensitivity.

    Evidence ChIP-seq, dCas9 enhancer blocking, luciferase reporters, site-directed mutagenesis of K223, subcellular fractionation, in vivo assays

    PMID:34489549 PMID:34866322 PMID:35349489

    Open questions at the time
    • Interplay between acetylation and SUMOylation on the same FOXK2 molecule not explored
    • Tissue specificity of enhancer-level regulation (e.g., IRE1α) not defined
  11. 2022 High

    Identification of PIAS4 as the SUMO E3 ligase for FOXK2 completed the SUMOylation pathway: PIAS4-mediated SUMOylation drives nuclear translocation and activates nucleotide de novo synthesis genes, while DNA damage suppresses this modification, explaining 5-FU chemoresistance.

    Evidence ChIP-seq, RNA-seq, SUMO modification assays, subcellular fractionation, in vivo functional assays

    PMID:36682222

    Open questions at the time
    • De-SUMOylation enzyme (SENP) for FOXK2 not identified
    • Whether DNA damage signals directly to PIAS4 or to FOXK2 to suppress SUMOylation unknown
  12. 2024 High

    Discovery that FBXO24 polyubiquitylates FOXK2 via its C-terminus for proteasomal degradation, and that PDK2 phosphorylates FOXK2 at T13/S30 via the FHA domain to enhance transcriptional activity in a positive feedback loop with glycolysis, revealed two new regulatory circuits controlling FOXK2 protein levels and metabolic output.

    Evidence Co-IP, domain mapping, in vitro kinase assay, ubiquitination assay, ChIP, luciferase reporters, Fbxo24 heterozygous mouse model

    PMID:38734828 PMID:38735474

    Open questions at the time
    • Signals triggering FBXO24-mediated degradation not identified
    • Whether PDK2 phosphorylation affects FOXK2 interaction with BAP1 or corepressors unknown
    • Mitochondrial function of FOXK2 detected by fractionation but mechanism undefined
  13. 2024 High

    KSHV ORF45 hijacks FOXK2's FHA domain through a phospho-Thr-containing linear motif to augment FOXK2 occupancy on late viral promoters, establishing FOXK2 as a host factor co-opted for herpesviral lytic gene expression.

    Evidence Co-IP, pulldown, mutagenesis of ORF45 interaction motif, ChIP, siRNA, viral gene expression assays

    PMID:39287387 PMID:39494902

    Open questions at the time
    • Whether other viruses exploit FOXK2's FHA domain unknown
    • Cellular consequences of ORF45 competition with BAP1 for FHA domain not tested
  14. 2025 High

    FOXK2 was shown to directly activate CCNB1/CDK1 and PPARγ to drive cardiomyocyte proliferation and adipogenesis, respectively, with PI3K/mTOR-dependent nuclear entry and positive feedback loops, broadening its role as a metabolic-proliferative transcription factor across differentiation contexts.

    Evidence Cardiomyocyte-specific KO, AAV9 OE, ChIP, MI model, adipogenic differentiation assays, pharmacological inhibitors

    PMID:39789420 PMID:40128196

    Open questions at the time
    • Tissue-specific cofactors determining target gene selection undefined
    • Whether FOXK1 and FOXK2 are functionally redundant in these contexts not fully resolved
  15. 2025 High

    Identification of FOXK2 mutations as causative for congenital myopathy with ptosis, with KO models showing impaired myogenic differentiation, disrupted mitochondrial homeostasis, and rescue by Coenzyme Q10, established the first Mendelian disease caused by FOXK2 deficiency.

    Evidence Whole exome sequencing in patients, zebrafish and mouse muscle-specific KO, ATAC-seq, mitochondrial assays, CoQ10 rescue

    PMID:40410591

    Open questions at the time
    • Specific FOXK2 target genes mediating CoQ10-responsive mitochondrial defect not fully enumerated
    • Genotype-phenotype correlation across different FOXK2 mutations not established
    • Whether congenital myopathy involves loss of metabolic or corepressor functions (or both) not dissected

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how FOXK2 selects among its multiple corepressor and coactivator complexes at individual loci; the direct Akt/mTOR phosphorylation sites controlling nuclear import; the structural basis of FHA domain interactions with BAP1, PDK2, and ORF45; and whether the mitochondrial pool of FOXK2 has a transcription-independent function.
  • No structural model of FOXK2 FHA domain with any partner
  • Direct phosphorylation sites for Akt-mediated nuclear import not mapped
  • Mitochondrial function of FOXK2 detected but mechanism undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0003677 DNA binding 7 GO:0060090 molecular adaptor activity 1
Localization
GO:0005634 nucleus 6 GO:0005739 mitochondrion 1 GO:0005829 cytosol 1
Pathway
R-HSA-74160 Gene expression (Transcription) 7 R-HSA-392499 Metabolism of proteins 5 R-HSA-1430728 Metabolism 4 R-HSA-162582 Signal Transduction 3 R-HSA-4839726 Chromatin organization 3 R-HSA-1266738 Developmental Biology 2 R-HSA-1640170 Cell Cycle 2
Partners
BAP1BARD1CBPFBXO24HCF1PDK2PIAS4SIRT1
Complex memberships
NCoR/SMRT corepressor complexNuRD complexPR-DUB (BAP1–ASXL)SIN3A corepressor complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 FOXK2 (originally called ILF) contains a forkhead DNA-binding domain sufficient to mediate DNA binding to purine-rich regulatory sequences in the HIV-1 LTR and IL2 promoter; the forkhead domain alone is sufficient for DNA binding. Gel retardation (EMSA), expression library screening, domain mapping Genomics Medium 1339390
2010 FOXK2 is phosphorylated by CDK1·cyclin B (and also CDK2·cyclin A) at serines 368 and 423 during mitosis; these phosphorylation events regulate FOXK2 protein stability and its activity as a transcriptional repressor, and expression of a mutant lacking these sites causes apoptosis. Cell cycle synchronization, CDK kinase assays, site-directed mutagenesis, transcriptional reporter assays The Journal of biological chemistry High 20810654
2010 The forkhead domain of FOXK2 binds G/T-mismatch DNA with higher affinity than matched consensus DNA; it also recognizes hypoxanthine/T and G/uracil mispairs; EMSA with anti-FOXK2 antibody confirmed FOXK2 is the G/T-mismatch binding activity in HL60 nuclear extracts. Expression library screening for mismatch DNA binding, EMSA, antibody supershift, recombinant domain binding assays Journal of biochemistry Medium 20097901
2011 FOXK2 binds genome-wide regulatory regions that are co-associated with AP-1 binding motifs and is required for efficient recruitment of AP-1 to chromatin and subsequent AP-1-dependent gene expression changes. ChIP-seq, genome-wide binding analysis, ChIP-qPCR, gene expression analysis after knockdown Molecular and cellular biology High 22083952
2014 FOXK2 binds the SIN3A and PR-DUB (BAP1-containing) complexes; FOXK2 recruits BAP1 to specific genomic loci via its forkhead-associated (FHA) domain, promotes local histone H2A deubiquitination, and thereby alters target gene activity. Co-immunoprecipitation, ChIP, histone deubiquitination assays, domain mapping Nucleic acids research High 24748658
2014 FOXK2 recruits BAP1 to target gene loci through its FHA domain, which recognizes phospho-Thr493 on BAP1; BAP1 in turn recruits HCF-1, forming a ternary FOXK2–BAP1–HCF-1 complex; BAP1 DUB activity (but not HCF-1 interaction) is required to repress FOXK2 target genes; BAP1 depletion causes Ring1B–Bmi1-dependent upregulation of these targets. Co-immunoprecipitation, pulldown, deubiquitinase activity assays, RNAi knockdown, epistasis with Ring1B-Bmi1 The Journal of biological chemistry High 25451922
2015 FOXK2 interacts with ERα and with BARD1 (of the BRCA1/BARD1 E3 ubiquitin ligase), acting as a scaffold to bring BRCA1/BARD1 and ERα together, thereby enhancing ubiquitin-mediated degradation of ERα and reducing its transcriptional activity; knockdown of both FOXK2 and ERα abolished the proliferative effect of FOXK2 KD. Co-immunoprecipitation, ubiquitination assays, reporter assays, siRNA knockdown, proliferation assays Scientific reports High 25740706
2015 FoxK2 knockdown in neural/proliferating cells decreases BrdU incorporation and H3 phosphorylation (proliferation markers), increases caspase 3 activity and cell death, upregulates pro-apoptotic Puma and Noxa, and increases p70S6K phosphorylation; rapamycin blocks p70S6K increase and synergizes with FoxK2 KD on proliferation but not apoptosis, indicating mTOR forms a compensatory feedback loop. siRNA knockdown, BrdU incorporation, caspase activity assay, flow cytometry, qRT-PCR, Western blot, rapamycin epistasis Journal of cellular physiology Medium 25216324
2016 FOXK2 interacts with transcription corepressor complexes NCoR/SMRT, SIN3A, NuRD, and REST/CoREST to repress a cohort of genes including HIF1β and EZH2, suppressing the hypoxic response; ERα transactivates FOXK2, and HIF1β/EZH2 reciprocally repress FOXK2 expression in a feedback loop. Co-immunoprecipitation, ChIP, gene expression analysis, luciferase reporter assays, KD/OE functional assays Cancer cell High 27773593
2018 FOXK2 is SUMOylated at lysines 527 and 633; SUMOylation-defective mutants (K527/633R) are unable to bind the FOXO3 promoter by ChIP and fail to upregulate FOXO3 transcription, reducing paclitaxel sensitivity, despite similar protein levels and subcellular localization to wild-type FOXK2. Site-directed mutagenesis of SUMO consensus sites, ChIP, cell viability/clonogenic assays, qRT-PCR, Western blot Oncogenesis High 29540677
2019 FOXK1 and FOXK2 induce aerobic glycolysis by transcriptionally upregulating glycolytic enzymes (hexokinase-2, phosphofructokinase, pyruvate kinase, lactate dehydrogenase) and pyruvate dehydrogenase kinases 1 and 4 (PDK1/4), while suppressing pyruvate dehydrogenase phosphatase 1 (PDP1), resulting in increased phosphorylation of pyruvate dehydrogenase E1α subunit and inhibition of mitochondrial pyruvate oxidation. KO/KD and overexpression in cell lines and primary human cells, metabolic flux assays, gene expression profiling, in vivo mouse experiments Nature High 30700909
2019 FoxK1 and FoxK2 nuclear translocation following insulin stimulation is dependent on the Akt–mTOR pathway, while cytoplasmic retention in basal state depends on GSK3; this translocation is reciprocal to FoxO1 nuclear-to-cytoplasmic translocation. Knockdown reduces lipid metabolism and cell proliferation genes and alters mitochondrial fatty acid metabolism. Subcellular fractionation, live-cell imaging of translocation, pharmacological inhibitors (Akt, mTOR, GSK3), siRNA knockdown, RNA-seq, metabolic assays Nature communications High 30952843
2021 FOXK2 directly regulates IRE1α (ERN1) expression by binding to an intronic regulatory enhancer element of the ERN1 gene, as shown by ChIP-seq; blocking this binding with dCas9 diminished IRE1α transcription; FOXK2-driven IRE1α upregulation leads to alternative XBP1 splicing and activation of stemness pathways in ovarian cancer stem cells. ChIP-seq, CRISPR/dCas9 enhancer blocking, RNA-seq, genetic depletion with stem cell functional assays The Journal of clinical investigation High 35349489
2021 FOXK2 is acetylated at K223 by the acetyltransferase CBP (CREB-binding protein) and deacetylated by SIRT1; cisplatin attenuates FOXK2–SIRT1 interaction; FOXK2 K223 acetylation reduces its nuclear localization and promotes mitotic catastrophe, enhancing chemosensitivity to cisplatin. Co-immunoprecipitation, site-directed mutagenesis (K223), Western blot for acetylation, subcellular fractionation, SIRT1 inhibitor experiments, in vitro and in vivo functional assays Journal of cellular and molecular medicine High 34866322
2021 FOXK2 transcriptionally activates VEGFA by binding directly to its promoter, promoting angiogenesis; VEGFA produced by FOXK2-expressing cells binds VEGFR1 as a compensatory mechanism when VEGFR2 is blocked, activating ERK, PI3K/AKT, and P38/MAPK; a positive feedback loop exists in which VEGFA/VEGFR1 signaling further promotes FOXK2-mediated VEGFA transcription. RNA-seq, ChIP-seq, ChIP, dual-luciferase reporter assay, functional angiogenesis assays, pharmacological VEGFR inhibition Oncogene High 34489549
2021 FOXK2 promotes AP-1-mediated transcription by being required for efficient recruitment of AP-1 to chromatin; FOXK2 binding regions genome-wide are co-associated with AP-1 binding motifs. ChIP-seq, ChIP-qPCR, gene expression analysis, functional assays with AP-1 pathway activation Nucleic acids research (2021 paper on ESC premarking) Medium 33434264
2022 FOXK2 is SUMOylated by PIAS4, which promotes FOXK2 nuclear translocation; nuclear FOXK2 then binds promoters of nucleotide de novo synthesis genes and activates their transcription; DNA damage suppresses FOXK2 SUMOylation; elevated FOXK2 SUMOylation promotes nucleotide synthesis and causes resistance to 5-FU. ChIP-seq, RNA-seq, luciferase promoter assay, SUMO modification assays, subcellular fractionation, in vitro and in vivo functional assays Drug resistance updates High 36682222
2023 FOXK2 is SUMOylated by PIAS4 leading to nuclear translocation and transcriptional activation of nucleotide synthetic genes; DNA damage represses this SUMOylation and reduces resistance to chemotherapy. ChIP-seq, RNA-seq, SUMO modification assays, subcellular fractionation Drug resistance updates High 36682222
2024 FOXK2 is polyubiquitylated by the SCF E3 ligase subunit FBXO24 via the FOXK2 carboxyl terminus (aa 428–478), leading to nuclear proteasomal degradation of FOXK2; FOXK2 is also detected within mitochondria and its depletion or expression of mutants lacking key C-terminal domains impairs mitochondrial function; Fbxo24 heterozygous mice show preserved mitochondrial function and FOXK2 levels during bacterial pneumonia. Co-immunoprecipitation, domain mapping, ubiquitination assays, subcellular fractionation (mitochondrial), in vivo mouse genetic model The Journal of biological chemistry High 38735474
2024 PDK2 directly binds the forkhead-associated (FHA) domain of FOXK2 and phosphorylates FOXK2 at Thr13 and Ser30, enhancing its transcriptional activity; FOXK2 transcriptionally regulates PDK2 expression, forming a positive feedback loop sustaining glycolysis in ovarian cancer cells. Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis, ChIP, luciferase reporter assay, in vitro and in vivo functional assays Oncogene High 38734828
2024 FOXK1 and FOXK2 are ORF45-binding proteins; ORF45 (KSHV immediate early tegument protein) interacts with the FHA domains of FOXK1 and FOXK2 through a conserved short linear serine/threonine-rich motif (a single threonine point mutation abolishes interaction); ORF45 augments FOXK1/2 occupancy on late viral gene promoters and their transcriptional activity to promote late KSHV lytic replication. Co-immunoprecipitation, pulldown, ChIP, site-directed mutagenesis of ORF45 interaction motif, viral gene expression assays, siRNA knockdown Journal of virology High 39287387 39494902
2025 Foxk1 and Foxk2 directly activate CCNB1 (cyclin B1) and CDK1 expression in cardiomyocytes; the resulting CCNB1/CDK1 complex facilitates G2/M transition; Foxk1/2 also upregulate HIF1α to enhance glycolysis and the pentose phosphate pathway, promoting cardiomyocyte proliferation; cardiomyocyte-specific knockout impairs neonatal heart regeneration after MI. Cardiomyocyte-specific KO, AAV9 overexpression, ChIP, cell cycle analysis, metabolic assays, myocardial infarction model Nature communications High 40128196
2025 FOXK2 mutations cause congenital myopathy with ptosis; FOXK2 deficiency impairs myogenic differentiation and disrupts mitochondrial homeostasis in muscle stem cells and C2C12 cells; FOXK2 directly regulates expression of mitochondrial function-related genes by modulating chromatin accessibility at its binding sites; Coenzyme Q10 treatment rescued mitochondrial function and skeletal muscle defects in Foxk2-deficient mice. Whole exome sequencing, zebrafish foxk2 KO, mouse muscle stem cell-specific KO, ATAC-seq, gene expression analysis, mitochondrial functional assays, rescue experiments EMBO molecular medicine High 40410591
2025 Foxk2 nuclear translocation during adipogenic differentiation is driven by PI3-kinase and mTOR signaling; once nuclear, Foxk2 binds the promoters of Pparγ1 and Pparγ2 to enhance their transcription; PPARγ1 and PPARγ2 reciprocally augment Foxk2 promoter transcriptional activity, forming a Foxk2–PPARγ positive feedback loop driving adipogenesis. Overexpression/knockdown, subcellular fractionation/nuclear translocation assays, PI3K and mTOR inhibitors, ChIP on Pparγ promoters, luciferase reporter assays, adipogenic differentiation assays Journal of cellular and molecular medicine High 39789420
2024 FOXK2 interacts with both mTOR and DRP1 (detected by co-immunoprecipitation); FOXK2 promotes phosphorylation of mTOR and upregulates CPT1A (fatty acid oxidation) while downregulating ACC1 and FASN (lipogenesis), thereby regulating lipid metabolic reprogramming in cervical cancer via the mTOR/DRP1 signaling axis. Co-immunoprecipitation, Western blot, OCR measurement, in vivo xenograft Frontiers in cell and developmental biology Medium 40641601

Source papers

Stage 0 corpus · 56 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 FOXK1 and FOXK2 regulate aerobic glycolysis. Nature 147 30700909
2019 FoxK1 and FoxK2 in insulin regulation of cellular and mitochondrial metabolism. Nature communications 87 30952843
2016 FOXK2 Elicits Massive Transcription Repression and Suppresses the Hypoxic Response and Breast Cancer Carcinogenesis. Cancer cell 84 27773593
2014 BRCA1-associated protein 1 (BAP1) deubiquitinase antagonizes the ubiquitin-mediated activation of FoxK2 target genes. The Journal of biological chemistry 74 25451922
2014 The forkhead transcription factor FOXK2 acts as a chromatin targeting factor for the BAP1-containing histone deubiquitinase complex. Nucleic acids research 67 24748658
2010 Cell cycle-dependent regulation of the forkhead transcription factor FOXK2 by CDK·cyclin complexes. The Journal of biological chemistry 63 20810654
2021 CircHIPK3 regulates pulmonary fibrosis by facilitating glycolysis in miR-30a-3p/FOXK2-dependent manner. International journal of biological sciences 59 34239356
2011 The forkhead transcription factor FOXK2 promotes AP-1-mediated transcriptional regulation. Molecular and cellular biology 57 22083952
2015 FOXK2 transcription factor suppresses ERα-positive breast cancer cell growth through down-regulating the stability of ERα via mechanism involving BRCA1/BARD1. Scientific reports 55 25740706
2019 FOXK2 Transcription Factor and Its Emerging Roles in Cancer. Cancers 48 30897782
2016 Sox9 mediated transcriptional activation of FOXK2 is critical for colorectal cancer cells proliferation. Biochemical and biophysical research communications 48 28007600
2020 Circular RNA Circ-ITCH Inhibits the Malignant Behaviors of Cervical Cancer by microRNA-93-5p/FOXK2 Axis. Reproductive sciences (Thousand Oaks, Calif.) 41 31993998
2017 Foxk2 inhibits non-small cell lung cancer epithelial-mesenchymal transition and proliferation through the repression of different key target genes. Oncology reports 41 28260088
2018 FOXK2 suppresses the malignant phenotype and induces apoptosis through inhibition of EGFR in clear-cell renal cell carcinoma. International journal of cancer 40 29368368
1992 Characterization and chromosomal mapping of the gene encoding the cellular DNA binding protein ILF. Genomics 38 1339390
2022 FOXK2 promotes ovarian cancer stemness by regulating the unfolded protein response pathway. The Journal of clinical investigation 34 35349489
2021 FOXK2 transcriptionally activating VEGFA induces apatinib resistance in anaplastic thyroid cancer through VEGFA/VEGFR1 pathway. Oncogene 28 34489549
2015 FoxK2 is required for cellular proliferation and survival. Journal of cellular physiology 28 25216324
2020 CircUBAP2 Inhibits Proliferation and Metastasis of Clear Cell Renal Cell Carcinoma via Targeting miR-148a-3p/FOXK2 Pathway. Cell transplantation 27 32425115
2018 SUMOylation modulates FOXK2-mediated paclitaxel sensitivity in breast cancer cells. Oncogenesis 25 29540677
2021 LncRNA SNHG7 Promotes the HCC Progression Through miR-122-5p/FOXK2 Axis. Digestive diseases and sciences 22 33738672
2023 FOXK2 affects cancer cell response to chemotherapy by promoting nucleotide de novo synthesis. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 20 36682222
2010 FOXK2 transcription factor is a novel G/T-mismatch DNA binding protein. Journal of biochemistry 19 20097901
2019 R. verniciflua and E. ulmoides Extract (ILF-RE) Protects against Chronic CCl₄-Induced Liver Damage by Enhancing Antioxidation. Nutrients 17 30759889
2020 FOXK2 downregulation suppresses EMT in hepatocellular carcinoma. Open medicine (Warsaw, Poland) 15 33313412
2019 Epigenetically Upregulated MicroRNA-602 Is Involved in a Negative Feedback Loop with FOXK2 in Esophageal Squamous Cell Carcinoma. Molecular therapy : the journal of the American Society of Gene Therapy 15 31401147
2025 Foxk1 and Foxk2 promote cardiomyocyte proliferation and heart regeneration. Nature communications 14 40128196
2021 The forkhead transcription factor FOXK2 premarks lineage-specific genes in human embryonic stem cells for activation during differentiation. Nucleic acids research 14 33434264
2022 FOXK2 promotes the proliferation of papillary thyroid cancer cell by down-regulating autophagy. Journal of Cancer 13 35154454
2022 Regulation and roles of FOXK2 in cancer. Frontiers in oncology 13 36172141
2021 The deacetylation of Foxk2 by Sirt1 reduces chemosensitivity to cisplatin. Journal of cellular and molecular medicine 13 34866322
2024 FOXK2 amplification promotes breast cancer development and chemoresistance. Cancer letters 10 38901667
2021 Mir-204 Regulates LPS-Induced A549 Cell Damage by Targeting FOXK2. Journal of healthcare engineering 8 34900201
2024 FOXK2 targeting by the SCF-E3 ligase subunit FBXO24 for ubiquitin mediated degradation modulates mitochondrial respiration. The Journal of biological chemistry 7 38735474
2024 Phosphorylation of FOXK2 at Thr13 and Ser30 by PDK2 sustains glycolysis through a positive feedback manner in ovarian cancer. Oncogene 6 38734828
2024 FOXK2 facilitates the airway remodeling during chronic asthma by promoting glycolysis in a SIRT2-dependent manner. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 6 38949649
2022 FOXK2 transcription factor and its roles in tumorigenesis (Review). Oncology letters 6 36380871
2024 Emerging roles of FOXK2 in cancers and metabolic disorders. Frontiers in oncology 5 38741782
2024 Exploiting the Warburg Effect: Co-Delivery of Metformin and FOXK2 siRNA for Ovarian Cancer Therapy. Small science 5 40212695
2023 FOXK2 regulates PFKFB3 in promoting glycolysis and tumorigenesis in multiple myeloma. Leukemia research 5 37356282
2025 Foxk2 Enhances Adipogenic Differentiation by Relying on the Transcriptional Activation of Peroxisome Proliferator-Activated Receptor Gamma. Journal of cellular and molecular medicine 3 39789420
2025 FOXK2 regulates fatty acid metabolism and promotes cervical cancer progression by activating the mTOR/DRP1 signaling axis. Frontiers in cell and developmental biology 3 40641601
2022 Genomic Aberrations Generate Fusion Gene FOXK2::TP63 and Activate NFKB1 in Cutaneous T-Cell Lymphoma. Biomedicines 3 36009586
2025 FOXK2 in skeletal muscle development: a new pathogenic gene for congenital myopathy with ptosis. EMBO molecular medicine 2 40410591
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
2024 The role of FOXK2-FBXO32 in breast cancer tumorigenesis: Insights into ribosome-associated pathways. Thoracic cancer 2 39552461
2023 FOXK2 amplification and overexpression promotes breast cancer development and chemoresistance. bioRxiv : the preprint server for biology 1 37398114
2012 ILF-3 is a regulator of the neural plate border marker Zic1 in chick embryos. Developmental dynamics : an official publication of the American Association of Anatomists 1 22639388
2026 pCancer and FOXK2 (Forkhead Box K2): Oncogenic and Tumor-Suppressive Roles of FOXK2 in Cancer. Biochemical genetics 0 41632365
2026 FOXK2/SH2D3A axis recruits EGFR to drive papillary thyroid cancer progression and confers sensitivity to EGFR inhibition. Naunyn-Schmiedeberg's archives of pharmacology 0 41984197
2025 Yiqi Yangyin Tongluo prescription targets lncRNA VIM-AS1 to regulate FOXK2/mTOR to promote autophagy and inhibit renal tubular epithelial cell apoptosis. Journal of food and drug analysis 0 40592335
2025 Targeting FOXK2 in triple-negative breast cancer: Role of the P53/MCAS1/miR-211-5p regulatory axis. Functional & integrative genomics 0 40944807
2025 CircRNA MALAT1/miR-96-5p/FOXK2 axis regulates choroidal neovascularization. Clinics (Sao Paulo, Brazil) 0 40997603
2023 Retracted: Mir-204 Regulates LPS-Induced A549 Cell Damage by Targeting FOXK2. Journal of healthcare engineering 0 37886320
2022 Erratum: FOXK2 promotes the proliferation of papillary thyroid cancer cell by down-regulating autophagy: Erratum. Journal of Cancer 0 36606195