Affinage

FOXK2

Forkhead box protein K2 · UniProt Q01167

Length
660 aa
Mass
69.1 kDa
Annotated
2026-06-09
56 papers in source corpus 28 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FOXK2 is a ubiquitously expressed forkhead transcription factor that binds DNA through its forkhead domain and acts as both an activator and repressor to coordinate cell proliferation, metabolic reprogramming, and lineage-specific gene programs (PMID:1339390, PMID:22083952, PMID:27773593). At chromatin it nucleates corepressor activity by recruiting the SIN3A, NCoR/SMRT, NuRD, and REST/CoREST complexes to repress targets such as HIF1β and EZH2, and it uses its forkhead-associated (FHA) domain to recruit the BAP1 PR-DUB deubiquitinase—engaging phospho-Thr493 of BAP1 and a downstream BAP1–HCF-1 ternary complex—to deubiquitinate histone H2A and antagonize Ring1B-Bmi1 at target loci (PMID:24748658, PMID:25451922, PMID:27773593). FOXK2 also activates gene expression, facilitating AP-1 recruitment to chromatin, and premarking lineage regulatory regions in embryonic stem cells ahead of differentiation (PMID:22083952, PMID:33434264). A central output is metabolic control: FOXK2 (with FOXK1) drives aerobic glycolysis by upregulating glycolytic enzymes and the pyruvate dehydrogenase kinases that suppress mitochondrial pyruvate oxidation, while also governing mitochondrial gene programs in differentiating muscle and lipid metabolic reprogramming (PMID:30700909, PMID:40410591, PMID:40641601). FOXK2 activity and localization are tightly tuned by post-translational modification: CDK1·cyclin B phosphorylation at Ser368/Ser423 controls its stability and repressor activity during mitosis (PMID:20810654); insulin–Akt–mTOR signaling drives nuclear translocation that is held in check by GSK3 in the basal state, reciprocal to FoxO1 (PMID:30952843); PIAS4-mediated SUMOylation at Lys527/Lys633 promotes nuclear entry and promoter binding (PMID:29540677, PMID:36682222); CBP acetylation versus SIRT1 deacetylation at Lys223 reciprocally controls nuclear distribution and chemosensitivity (PMID:34866322); and the FBXO24-SCF E3 ligase mediates nuclear polyubiquitylation and degradation (PMID:38735474). Through these activities FOXK2 supports proliferation and survival—its loss triggers caspase-dependent apoptosis and upregulation of Puma/Noxa—and contributes to cardiomyocyte cell-cycle re-entry and neonatal heart regeneration (PMID:25216324, PMID:40128196).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1992 Medium

    Established that FOXK2 is a sequence-specific DNA-binding protein, defining its forkhead domain as the DNA-binding module on purine-rich regulatory elements.

    Evidence Gel retardation and cDNA characterization with domain mapping on HIV-1 LTR and IL2 promoter sequences

    PMID:1339390

    Open questions at the time
    • No genome-wide binding map at this stage
    • Cellular function and target genes undefined
    • No regulation or partner data
  2. 2010 High

    Defined FOXK2 as a cell-cycle-regulated factor whose mitotic CDK phosphorylation controls its stability and repressor activity, and whose disruption triggers apoptosis.

    Evidence Cell-cycle synchronization, in vitro kinase assays, Ser368/Ser423 mutagenesis, and reporter assays; separate EMSA work identified G/T-mismatch DNA binding

    PMID:20097901 PMID:20810654

    Open questions at the time
    • Downstream apoptotic effectors of phospho-mutant not mapped
    • Biological role of mismatch DNA binding unresolved
    • Target genes during mitosis not enumerated
  3. 2011 High

    Placed FOXK2 in a genome-wide regulatory context, showing it co-localizes with AP-1 motifs and facilitates AP-1 chromatin recruitment to activate gene expression.

    Evidence ChIP-seq, genome-wide binding analysis, and gene expression profiling

    PMID:22083952

    Open questions at the time
    • Mechanism of AP-1 cooperativity not structurally defined
    • Distinction of activator vs repressor target sets incomplete
  4. 2014 High

    Revealed FOXK2 as a chromatin-modifying hub that recruits corepressor and deubiquitinase complexes, explaining how it represses target loci.

    Evidence Co-IP, ChIP, DUB activity mutants, and histone modification assays defining FHA–phospho-Thr493 recruitment of BAP1 and the BAP1–HCF-1 complex antagonizing Ring1B-Bmi1

    PMID:24748658 PMID:25451922

    Open questions at the time
    • Determinants of complex choice at a given locus unclear
    • Structural basis of FHA–phospho-Thr493 not solved
  5. 2015 Medium

    Connected FOXK2 to E3-ligase scaffolding and growth control, showing it promotes ERα degradation and that its loss arrests proliferation and triggers apoptosis with Puma/Noxa induction.

    Evidence Co-IP, ubiquitination assays, siRNA knockdown with BrdU/caspase-3 readouts and rapamycin epistasis

    PMID:25216324 PMID:25740706

    Open questions at the time
    • Scaffold mechanism for BRCA1/BARD1-mediated ERα ubiquitylation not detailed
    • mTOR/p70S6K compensatory loop mechanism partially defined
  6. 2016 High

    Defined the full corepressor repertoire of FOXK2 and embedded it in transcriptional feedback circuits with ERα, HIF1β, and EZH2.

    Evidence Multiple Co-IPs identifying NCoR/SMRT, SIN3A, NuRD, REST/CoREST; ChIP and reporter assays; promoter ChIP showing SOX9 activates FOXK2

    PMID:27773593 PMID:28007600

    Open questions at the time
    • Context selectivity of corepressor recruitment unresolved
    • Upstream activator hierarchy across tissues unclear
  7. 2017 Medium

    Showed FOXK2 directly represses EMT and proliferation programs (N-cadherin, Snail, cyclin D1, CDK4), framing a tumor-suppressive transcriptional output in some contexts.

    Evidence ChIP-seq, qChIP, luciferase reporters, and invasion/proliferation assays in NSCLC cells

    PMID:28260088

    Open questions at the time
    • Cofactors mediating repression at these promoters not identified
    • Context-dependence vs oncogenic roles elsewhere unreconciled
  8. 2019 High

    Established FOXK2 as a master driver of aerobic glycolysis downstream of insulin signaling, with localization gated by Akt-mTOR versus GSK3 reciprocal to FoxO1.

    Evidence Knockdown/overexpression in cells and in vivo, metabolic flux assays, and pathway-inhibitor subcellular fractionation/immunofluorescence

    PMID:30700909 PMID:30952843

    Open questions at the time
    • Direct nuclear import machinery downstream of mTOR not defined
    • Tissue-specific metabolic target sets only partially mapped
  9. 2021 High

    Demonstrated multilayer PTM control of FOXK2 nuclear function and chemosensitivity, and expanded its activator targets to enhancers and angiogenic/stem programs.

    Evidence SUMOylation-site mutants with ChIP (Lys527/633); CBP/SIRT1 K223 acetylation with localization and cisplatin assays; dCas9 enhancer blocking at ERN1; VEGFA promoter ChIP-seq; ESC ChIP-seq premarking

    PMID:29540677 PMID:33434264 PMID:34489549 PMID:34866322 PMID:35349489

    Open questions at the time
    • How distinct PTMs are integrated on a single FOXK2 molecule unknown
    • Relationship between enhancer premarking and later activation mechanistically incomplete
  10. 2022 High

    Identified PIAS4 as the SUMO ligase that drives FOXK2 nuclear translocation to activate nucleotide synthesis genes, linking FOXK2 SUMOylation to chemoresistance.

    Evidence ChIP-seq, RNA-seq, SUMOylation and luciferase assays with DNA-damage modulation and in vivo 5-FU resistance

    PMID:36682222

    Open questions at the time
    • DNA-damage signal that represses SUMOylation not pinpointed
    • SUMO-dependent import receptor unidentified
  11. 2024 High

    Mapped FOXK2 degradation and an FHA-domain interaction repertoire (kinase, viral, and mitochondrial), broadening its regulatory and effector landscape.

    Evidence FBXO24-SCF Co-IP/ubiquitination with mitochondrial localization (mouse model); PDK2 FHA binding/Thr13-Ser30 phosphorylation feedback; KSHV ORF45 FHA-motif binding at viral promoters; SIRT2 rescue of EMT/glycolysis; PPARγ adipogenic activation

    PMID:38734828 PMID:38735474 PMID:38949649 PMID:39287387 PMID:39494902 PMID:39789420

    Open questions at the time
    • Functional role of mitochondrial FOXK2 pool only partly defined
    • How FHA domain discriminates among diverse phospho-partners unclear
  12. 2025 High

    Extended FOXK2 to organ regeneration and stem-cell differentiation, showing it drives cardiomyocyte cell-cycle re-entry and controls mitochondrial gene programs via chromatin accessibility.

    Evidence Cardiomyocyte- and muscle-stem-cell-specific knockouts with ChIP/ATAC-seq, AAV9 rescue, infarction and differentiation models, plus mTOR/DRP1 lipid-metabolism axis in cancer

    PMID:40128196 PMID:40410591 PMID:40641601

    Open questions at the time
    • Direct vs indirect control of mitochondrial gene chromatin not fully separated
    • Regenerative role tissue-restricted; human translation untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How FOXK2 selects between activating and repressive outputs at a given locus, and how its many PTMs and FHA-mediated interactions are integrated into context-specific programs, remains unresolved.
  • No structural model integrating PTM state with cofactor choice
  • Rules governing activator vs corepressor recruitment undefined
  • Physiological role of mitochondrial FOXK2 unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 4 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 4 GO:0005739 mitochondrion 2 GO:0005829 cytosol 1
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-4839726 Chromatin organization 3 R-HSA-1430728 Metabolism 2 R-HSA-162582 Signal Transduction 2 R-HSA-1640170 Cell Cycle 2 R-HSA-5357801 Programmed Cell Death 1
Partners
BAP1BARD1ERΑFBXO24PDK2PIAS4SIN3ASIRT1
Complex memberships
FOXK2–BAP1–HCF-1 (PR-DUB) complex

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 FOXK2 (then called ILF) was identified as a DNA-binding protein containing a forkhead domain; the forkhead domain is sufficient to mediate DNA binding to purine-rich regulatory sequences in the HIV-1 LTR and IL2 promoter. Gel retardation assay, cDNA characterization, chromosomal mapping Genomics Medium 1339390
2010 FOXK2 is phosphorylated by CDK1·cyclin B (primarily) and CDK2·cyclin A during mitosis; two phosphorylation sites, Ser368 and Ser423, regulate FOXK2 stability and its activity as a transcriptional repressor. Expression of a CDK phosphorylation-site mutant lacking these sites causes apoptosis. Cell cycle synchronization, kinase assays, site-directed mutagenesis, phosphorylation site mapping, transcriptional reporter assays The Journal of biological chemistry High 20810654
2010 FOXK2 binds G/T-mismatch DNA through its forkhead domain with higher affinity than matched consensus DNA; it also recognizes hypoxanthine/T and G/uracil mismatches, identifying it as a novel mismatch DNA-binding protein. Electrophoretic mobility shift assay (EMSA), cDNA library screening, recombinant domain binding assays Journal of biochemistry Medium 20097901
2011 FOXK2 promotes AP-1-dependent gene expression by facilitating the recruitment of AP-1 to chromatin; FOXK2 binding regions across the genome are frequently co-associated with AP-1 binding motifs. ChIP-seq, genome-wide binding analysis, gene expression profiling, chromatin recruitment assays Molecular and cellular biology High 22083952
2014 FOXK2 binds the SIN3A and PR-DUB (BAP1-containing) complexes; FOXK2 recruits BAP1 to DNA via its forkhead-associated (FHA) domain, promotes local histone H2A deubiquitination, and causes changes in target gene activity. Co-immunoprecipitation, ChIP, histone modification assays, gene expression analysis Nucleic acids research High 24748658
2014 FOXK2 recruits BAP1 to target gene loci through its FHA domain, which interacts with phospho-Thr493 on BAP1; BAP1 in turn recruits HCF-1, forming a ternary complex (FOXK2–BAP1–HCF-1). BAP1 represses FOXK2 target genes in a manner requiring its deubiquitinase (DUB) activity but not HCF-1 interaction. BAP1 antagonizes the Ring1B-Bmi1 E3 ubiquitin ligase (H2A ubiquitination) at these loci. Co-immunoprecipitation, chromatin immunoprecipitation, siRNA knockdown, DUB activity mutant analysis The Journal of biological chemistry High 25451922
2015 FOXK2 interacts with ERα and BARD1 (part of the BRCA1/BARD1 E3 ubiquitin ligase), acting as a scaffold to promote ubiquitin-mediated degradation of ERα, thereby reducing ERα transcriptional activity and inhibiting proliferation of ERα-positive breast cancer cells. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, transcriptional reporter assays, cell proliferation assays Scientific reports Medium 25740706
2015 Knockdown of FoxK2 in proliferating cells reduces BrdU incorporation and H3 phosphorylation (proliferation arrest), and in the absence of growth factors causes caspase-3 activation and cell death. FoxK2 loss upregulates pro-apoptotic Bcl-2 family members Puma and Noxa. mTOR/p70S6K provides a compensatory feedback loop, as rapamycin synergizes with FoxK2 knockdown to further reduce H3 phosphorylation. siRNA knockdown, BrdU incorporation, flow cytometry, caspase-3 activity assay, qRT-PCR, rapamycin treatment Journal of cellular physiology Medium 25216324
2016 FOXK2 interacts with transcription corepressor complexes NCoR/SMRT, SIN3A, NuRD, and REST/CoREST to repress target genes including HIF1β and EZH2. FOXK2 is transcriptionally activated by ERα, and repressed in a feedback loop by HIF1β/EZH2. Co-immunoprecipitation, ChIP, gene expression profiling, luciferase reporter assays, functional cell assays Cancer cell High 27773593
2016 SOX9 transcriptionally activates FOXK2 by directly binding to its promoter in colorectal cancer cells. ChIP, luciferase reporter assay, siRNA knockdown, qRT-PCR Biochemical and biophysical research communications Medium 28007600
2017 FOXK2 directly suppresses N-cadherin and Snail expression (repressing EMT) and suppresses cyclin D1 and CDK4 expression (inhibiting proliferation) in NSCLC cells, as determined by ChIP-seq and luciferase reporter assays. ChIP-seq, qChIP, luciferase reporter assays, lentiviral overexpression/knockdown, cell invasion and proliferation assays Oncology reports Medium 28260088
2018 SUMOylation of FOXK2 at Lys527 and Lys633 is required for its transcriptional activity and ability to bind the FOXO3 promoter; SUMOylation-defective mutants (K527/633R or E529/635A) lose the ability to mediate paclitaxel cytotoxicity and fail to occupy the FOXO3 promoter despite normal protein levels and subcellular localization. Site-directed mutagenesis, ChIP, cell viability assays, clonogenic assays, subcellular fractionation Oncogenesis High 29540677
2019 FOXK1 and FOXK2 induce aerobic glycolysis by transcriptionally upregulating glycolytic enzymes (hexokinase-2, phosphofructokinase, pyruvate kinase, lactate dehydrogenase) and suppressing pyruvate oxidation in mitochondria by increasing pyruvate dehydrogenase kinases 1 and 4 and suppressing pyruvate dehydrogenase phosphatase 1, leading to increased phosphorylation of the E1α subunit of pyruvate dehydrogenase complex and diversion of pyruvate to lactate. Knockdown/overexpression in cell lines and in vivo models, metabolic flux assays, gene expression profiling, primary human cell studies Nature High 30700909
2019 FoxK2 (and FoxK1) translocate from cytoplasm to nucleus following insulin stimulation; this nuclear translocation is dependent on the Akt-mTOR pathway, while cytoplasmic localization in the basal state is dependent on GSK3. This is reciprocal to FoxO1 nuclear-to-cytoplasmic translocation after insulin. Knockdown of FoxK1/FoxK2 in liver cells downregulates cell cycle/lipid metabolism genes and upregulates apoptosis genes, resulting in decreased proliferation and altered mitochondrial fatty acid metabolism. Subcellular fractionation, immunofluorescence, pathway inhibitor studies (Akt, mTOR, GSK3), siRNA knockdown, gene expression profiling, metabolic assays Nature communications High 30952843
2021 FOXK2 directly regulates IRE1α (ERN1) expression by binding to an intronic regulatory enhancer of ERN1; FOXK2-driven IRE1α upregulation leads to alternative XBP1 splicing and activation of stemness pathways in ovarian cancer stem cells. Blocking FOXK2 binding to this enhancer with dCas9 diminishes IRE1α transcription. ChIP-seq, CRISPR dCas9 enhancer blocking, RNA-seq, gene expression validation, tumor initiation assays The Journal of clinical investigation High 35349489
2021 FOXK2 is acetylated at Lys223 by the acetyltransferase CBP (cAMP response element binding protein); SIRT1 deacetylates FOXK2 at K223. Acetylation of K223 reduces nuclear localization of FOXK2 and promotes mitotic catastrophe, enhancing chemosensitivity to cisplatin. Cisplatin attenuates the FOXK2-SIRT1 interaction, leading to increased FOXK2 acetylation. Co-immunoprecipitation, site-directed mutagenesis (K223), subcellular fractionation, SIRT1 inhibitor treatment, in vitro and in vivo drug sensitivity assays Journal of cellular and molecular medicine High 34866322
2021 FOXK2 transcriptionally activates VEGFA by directly binding the VEGFA promoter, promoting angiogenesis. FOXK2-induced VEGFA binds VEGFR1 as a compensatory mechanism when VEGFR2 is blocked, activating ERK, PI3K/AKT, and P38/MAPK signaling, thereby conferring resistance to VEGFR2 inhibitor (apatinib). This constitutes a positive feedback loop: VEGFA/VEGFR1 signaling further promotes FOXK2-mediated VEGFA transcription. ChIP-seq, RNA-seq, ChIP, dual-luciferase reporter, VEGFR1 inhibition, in vitro angiogenesis assays Oncogene High 34489549
2021 FOXK2 premarks lineage-specific regulatory regions in human embryonic stem cells (ESCs) before differentiation; its binding at thousands of regulatory regions is associated with active histone marks and predicts regions activated during neural precursor cell (NPC) differentiation. FOXK transcription factors have a role in gene activation during NPC differentiation. Genome-wide ChIP-seq in ESCs and differentiated cell types, histone mark analysis, FOXK2 knockdown during NPC differentiation Nucleic acids research Medium 33434264
2022 FOXK2 is SUMOylated by PIAS4, which drives FOXK2 nuclear translocation, enabling it to bind promoters of nucleotide de novo synthesis genes and activate their transcription. DNA damage represses FOXK2 SUMOylation, and elevated FOXK2 SUMOylation promotes resistance to 5-FU in hepatocellular carcinoma. ChIP-seq, RNA-seq, luciferase promoter assay, SUMOylation assays, nuclear fractionation, DNA damage treatment, in vitro and in vivo drug resistance assays Drug resistance updates High 36682222
2024 FOXK2 is targeted for ubiquitin-mediated proteasomal degradation in the nucleus by the SCF E3 ligase subunit FBXO24, which binds FOXK2's carboxyl terminus (aa 428–478) and mediates multisite polyubiquitylation. FOXK2 is also detected within mitochondria, and its depletion or expression of carboxy-terminal mutants impairs mitochondrial function. Co-immunoprecipitation, ubiquitination assays, domain-deletion mutants, subcellular fractionation/mitochondrial localization, Fbxo24 heterozygous mouse model, bacterial pneumonia 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 FOXK2 transcriptional activity. FOXK2 in turn transcriptionally regulates PDK2 expression, forming a positive feedback loop that sustains glycolysis in ovarian cancer cells. Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis (Thr13, Ser30), ChIP, luciferase reporter assay, cell proliferation and migration assays, in vivo xenograft Oncogene High 38734828
2024 FOXK2 binds to the KSHV immediate-early tegument protein ORF45 via its forkhead-associated (FHA) domain, which recognizes a conserved serine/threonine-rich short linear motif in ORF45. ORF45 augments FOXK2 occupancy at late viral gene promoters and enhances FOXK2 transcriptional activity, promoting late KSHV lytic gene expression and virion production. Co-immunoprecipitation, point mutagenesis of ORF45 threonine motif, ChIP at viral promoters, siRNA knockdown of FOXK1/K2, lytic reactivation assays Journal of virology High 39287387 39494902
2024 FOXK2 promotes adipogenic differentiation of bone marrow stromal cells by directly binding to the promoters of PPARγ1 and PPARγ2 and enhancing their transcriptional activation. Nuclear translocation of Foxk2 during adipogenic stimulation is dependent on PI3-kinase and mTOR signaling. A Foxk2–PPARγ positive feedback loop drives adipogenesis. ChIP, luciferase reporter assays, overexpression/knockdown, nuclear fractionation, pathway inhibitor studies Journal of cellular and molecular medicine Medium 39789420
2024 FOXK2 interacts with SIRT2, and SIRT2 overexpression rescues the inhibition of EMT and glycolysis caused by FOXK2 knockdown in TGF-β1-treated bronchial epithelial cells, establishing that FOXK2 regulates EMT and glycolysis in a SIRT2-dependent manner. Co-immunoprecipitation, siRNA knockdown, SIRT2 overexpression rescue, EMT marker and glycolysis enzyme expression assays FASEB journal Medium 38949649
2025 Foxk1 and Foxk2 directly activate CCNB1 and CDK1 transcription, forming the CCNB1/CDK1 complex that facilitates G2/M transition and cardiomyocyte cell cycle progression. They also upregulate HIF1α expression to enhance glycolysis and the pentose phosphate pathway, further supporting cardiomyocyte proliferation. Cardiomyocyte-specific knockout of Foxk2 impairs neonatal heart regeneration after myocardial infarction. Cardiomyocyte-specific knockout, AAV9-mediated overexpression, ChIP (direct CCNB1/CDK1 promoter binding), in vivo myocardial infarction model, cell cycle analysis Nature communications High 40128196
2025 FOXK2 deficiency in skeletal muscle stem cells impairs myogenic differentiation and disrupts mitochondrial homeostasis. FOXK2 directly regulates the expression of mitochondrial function-related genes by modulating chromatin accessibility at its binding sites. Muscle stem cell (MuSC)-specific Foxk2 knockout in mice, zebrafish foxk2 morpholino knockdown, ATAC-seq/omics analysis of chromatin accessibility, C2C12 differentiation assays, coenzyme Q10 rescue EMBO molecular medicine Medium 40410591
2025 FOXK2 interacts with mTOR and DRP1 (co-immunoprecipitation), and promotes phosphorylation of mTOR. Via the mTOR/DRP1 signaling axis, FOXK2 upregulates CPT1A (fatty acid oxidation) while downregulating ACC1 and FASN (lipogenesis), driving lipid metabolic reprogramming in cervical cancer cells. Co-immunoprecipitation, Western blot for phospho-mTOR, overexpression/knockdown, xenograft in vivo model 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 148 30700909
2019 FoxK1 and FoxK2 in insulin regulation of cellular and mitochondrial metabolism. Nature communications 89 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 75 25451922
2014 The forkhead transcription factor FOXK2 acts as a chromatin targeting factor for the BAP1-containing histone deubiquitinase complex. Nucleic acids research 68 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 35 35349489
2021 FOXK2 transcriptionally activating VEGFA induces apatinib resistance in anaplastic thyroid cancer through VEGFA/VEGFR1 pathway. Oncogene 29 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
2025 Foxk1 and Foxk2 promote cardiomyocyte proliferation and heart regeneration. Nature communications 16 40128196
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
2021 The forkhead transcription factor FOXK2 premarks lineage-specific genes in human embryonic stem cells for activation during differentiation. Nucleic acids research 14 33434264
2021 The deacetylation of Foxk2 by Sirt1 reduces chemosensitivity to cisplatin. Journal of cellular and molecular medicine 14 34866322
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
2024 FOXK2 amplification promotes breast cancer development and chemoresistance. Cancer letters 10 38901667
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 8 38949649
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
2022 FOXK2 transcription factor and its roles in tumorigenesis (Review). Oncology letters 7 36380871
2024 Phosphorylation of FOXK2 at Thr13 and Ser30 by PDK2 sustains glycolysis through a positive feedback manner in ovarian cancer. Oncogene 6 38734828
2024 Emerging roles of FOXK2 in cancers and metabolic disorders. Frontiers in oncology 6 38741782
2023 FOXK2 regulates PFKFB3 in promoting glycolysis and tumorigenesis in multiple myeloma. Leukemia research 6 37356282
2024 Exploiting the Warburg Effect: Co-Delivery of Metformin and FOXK2 siRNA for Ovarian Cancer Therapy. Small science 5 40212695
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

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