Affinage

FOXO1

Forkhead box protein O1 · UniProt Q12778

Round 2 corrected
Length
655 aa
Mass
69.7 kDa
Annotated
2026-04-28
130 papers in source corpus 44 papers cited in narrative 44 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FOXO1 is a forkhead-family transcription factor that serves as a central integrator of insulin/PI3K/Akt signaling with metabolic gene regulation, cell-cycle control, apoptosis, autophagy, and inflammatory programs across diverse cell types. Akt directly phosphorylates FOXO1 at Thr-24, Ser-256, and Ser-319, triggering nuclear exclusion, Skp2-mediated ubiquitination, and proteasomal degradation; additional kinases (CK1, DYRK1A, NLK, PAK1) and the phosphatase SCP4 fine-tune its subcellular localization, while CBP-mediated acetylation attenuates DNA binding and SIRT1/SIRT2-mediated deacetylation restores transcriptional activity or redirects FOXO1 to a cytoplasmic Atg7-dependent autophagy pathway, and PRMT1-mediated arginine methylation antagonizes Akt phosphorylation (PMID:10358014, PMID:13679577, PMID:15668399, PMID:14710188, PMID:15220471, PMID:16076959, PMID:18951090, PMID:20543840, PMID:28851713). In the nucleus, FOXO1 binds insulin-response elements to activate gluconeogenic genes (G6Pase, PEPCK), pro-apoptotic targets (FasL, PUMA, GADD45α), and immune-regulatory genes (TLR4, CCR7, IL-9), while repressing D-type cyclins, MYC, and eNOS to enforce cell-cycle arrest, endothelial quiescence, and metabolic restraint (PMID:11696581, PMID:12150827, PMID:26735015, PMID:21045807, PMID:25786691, PMID:16100571). Foxo1-null mice die at ~E11 from angiogenic defects, and tissue-specific deletions in liver, endothelium, macrophages, intestinal epithelium, and immune cells demonstrate non-redundant roles in gluconeogenesis, vascular remodeling, inflammatory polarization, goblet cell autophagy, and T-cell differentiation (PMID:15184386, PMID:22147007, PMID:35700043, PMID:34287641, PMID:29339772).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1999 High

    Identification of Akt as the direct kinase for FOXO1 at three conserved sites established the core mechanism by which insulin/PI3K signaling inactivates FOXO1 transcriptional activity and triggers apoptosis when this regulation is lost.

    Evidence In vitro kinase assay with purified Akt, alanine-substitution mutagenesis, reporter and apoptosis assays in mammalian cells

    PMID:10358014 PMID:10358075

    Open questions at the time
    • Structural basis of Akt–FOXO1 interaction not resolved
    • In vivo phosphorylation kinetics not determined
  2. 1999 High

    Demonstration that FOXO1 binds insulin-response sequences and activates IRS-containing promoters defined it as a transcription factor directly mediating insulin-responsive gene regulation.

    Evidence In vitro DNA-binding assay and luciferase reporter in mammalian cells

    PMID:10358014 PMID:10358075

    Open questions at the time
    • Genome-wide binding profile not yet mapped
    • Endogenous target genes not identified at this stage
  3. 2001 High

    Gain- and loss-of-function experiments in hepatocytes established FOXO1 as the mediator of insulin regulation of gluconeogenic genes (G6Pase, PEPCK), connecting FOXO1 phosphorylation to whole-body glucose homeostasis.

    Evidence Adenoviral FOXO1 transduction and dominant-negative mutant in primary hepatocytes and kidney epithelial cells

    PMID:11696581

    Open questions at the time
    • Liver-specific in vivo deletion not yet performed
    • Relative contribution of FOXO1 versus other FOXO paralogs in hepatic gluconeogenesis unknown
  4. 2001 High

    Discovery that DYRK1A phosphorylates FOXO1 at Ser-329 to promote nuclear exclusion revealed a PI3K-independent input controlling FOXO1 activity.

    Evidence Purified kinase from skeletal muscle, co-IP, nuclear co-localization, site-directed mutagenesis

    PMID:11311120

    Open questions at the time
    • Physiological contexts requiring DYRK1A–FOXO1 regulation not defined
    • In vivo significance not validated with DYRK1A knockout
  5. 2002 High

    ChIP-validated occupancy of cyclin D promoters showed FOXO1 enforces cell-cycle arrest through transcriptional repression of D-type cyclins rather than solely through gene activation, broadening the mechanistic repertoire.

    Evidence Transcriptional profiling, ChIP, cell-cycle and transformation assays

    PMID:12150827

    Open questions at the time
    • Mechanism of transcriptional repression (corepressor identity) not determined
  6. 2003 High

    Reconstitution of phosphorylation-dependent ubiquitination and proteasomal degradation of FOXO1 established a two-step inactivation model (nuclear exclusion then degradation) downstream of insulin/Akt, with Skp2 identified as the E3 ligase.

    Evidence In vitro and in vivo ubiquitination assays with proteasome inhibitors and phospho-site mutants; Skp2 co-IP and in vitro ubiquitination

    PMID:13679577 PMID:15668399

    Open questions at the time
    • Whether additional E3 ligases target FOXO1 in specific tissues not resolved
    • Deubiquitinases for FOXO1 not identified
  7. 2004 High

    CK1-mediated phosphorylation at Ser-322/325 was shown to cooperate with Akt phosphorylation to drive nuclear exclusion, revealing multisite phosphorylation as a combinatorial regulatory code.

    Evidence CK1 inhibitor D4476, phospho-specific analysis, nuclear/cytoplasmic fractionation in hepatoma cells

    PMID:14710188

    Open questions at the time
    • CK1 isoform specificity not fully determined
    • Interplay with DYRK1A and NLK phosphorylation not tested
  8. 2004 High

    Foxo1-null embryonic lethality at ~E11 with angiogenic defects established FOXO1 as essential for vascular development and endothelial VEGF responses.

    Evidence Constitutive Foxo1 knockout mice, ES-cell-derived endothelial differentiation assay

    PMID:15184386

    Open questions at the time
    • Downstream transcriptional targets mediating the vascular phenotype not fully defined at this stage
  9. 2004 High

    Demonstration that SIRT1 deacetylates FOXO1 at CBP-acetylated lysines and is recruited to FOXO1 target promoters established the acetylation/deacetylation switch as a major regulatory axis modulating FOXO1 transcriptional output.

    Evidence In vitro deacetylation with purified SIRT1, ChIP on MnSOD/p27 promoters, catalytic-dead mutant control

    PMID:15220471

    Open questions at the time
    • Context-dependent selection of FOXO1 targets by acetylation state not systematically mapped
  10. 2005 High

    Biochemical reconstitution showed CBP acetylation at Lys-242/245/262 attenuates FOXO1 DNA binding by charge neutralization and sensitizes FOXO1 to Akt phosphorylation, revealing bidirectional crosstalk between acetylation and phosphorylation.

    Evidence In vitro DNA binding and kinase assays with acetylation-mimicking and acetylation-deficient mutants

    PMID:16076959

    Open questions at the time
    • In vivo stoichiometry of acetylated versus unacetylated FOXO1 unknown
  11. 2005 High

    Discovery that FOXO1 forms a complex with PML and SIRT1 in pancreatic beta cells to activate NeuroD/MafA transcription under oxidative stress revealed a tissue-specific protective function coupling acetylation to PML body localization.

    Evidence Co-IP of FoxO1–PML–SIRT1 complex, acetylation mutants, transgenic mice with beta-cell phenotyping

    PMID:16154098

    Open questions at the time
    • Whether PML–SIRT1–FOXO1 complex operates in non-beta-cell contexts not tested
  12. 2005 High

    Beta-catenin was identified as a direct FOXO co-activator under oxidative stress, conserved from C. elegans to mammals, linking Wnt pathway components to FOXO-dependent stress responses.

    Evidence Co-IP, reporter assay, C. elegans genetic epistasis (BAR-1/DAF-16)

    PMID:15905404

    Open questions at the time
    • Competition between TCF/LEF and FOXO for beta-catenin binding not quantitatively resolved
  13. 2006 High

    Liver-specific constitutively active FOXO1 transgenics demonstrated that FOXO1 globally coordinates hepatic metabolism by activating gluconeogenesis while suppressing glycolytic, lipogenic, and pentose phosphate pathway genes.

    Evidence Transgenic mice with liver-specific active FoxO1, gene array, adenoviral hepatocyte transduction, metabolic phenotyping

    PMID:16492665

    Open questions at the time
    • Direct versus indirect transcriptional targets within suppressed metabolic programs not distinguished
  14. 2008 High

    PRMT1-mediated methylation at Arg-248/250 was shown to directly block Akt phosphorylation at Ser-253, establishing arginine methylation as a third post-translational code that antagonizes the Akt-ubiquitination axis.

    Evidence In vitro methylation and kinase assays, PRMT1 siRNA, polyubiquitination assay, apoptosis assay

    PMID:18951090

    Open questions at the time
    • Physiological stimuli triggering PRMT1-dependent FOXO1 methylation not defined
    • Demethylase not identified
  15. 2010 High

    ChIP-Seq in macrophages revealed FOXO1 occupancy at enhancer-like elements within TLR4 and downstream innate immune genes, with TLR4 activation feeding back through Akt to inactivate FOXO1—establishing a self-limiting inflammatory circuit.

    Evidence ChIP-Seq, FoxO1 knockout macrophages, reporter assays, cytokine measurements

    PMID:21045807

    Open questions at the time
    • Precise chromatin remodeling events at FOXO1-bound enhancers not characterized
  16. 2010 High

    Cytoplasmic acetylated FOXO1 was shown to bind Atg7 and induce autophagy independently of transcription, revealing a non-nuclear tumor-suppressive function mediated by SIRT2 dissociation.

    Evidence Co-IP (FoxO1–Atg7), transcription-deficient mutants, autophagy assays, SIRT2 interaction studies, xenograft tumor model

    PMID:20543840

    Open questions at the time
    • Structural basis of acetylated FOXO1–Atg7 interaction unknown
    • Relative contribution of transcriptional versus cytoplasmic autophagy pathways in different tissues not quantified
  17. 2011 High

    Liver-specific Foxo1 deletion confirmed its non-redundant role in gluconeogenesis in vivo, while combined Foxo1/Foxo3 deletion additionally derepressed lipogenesis, genetically separating paralog-specific metabolic functions.

    Evidence Cre/LoxP conditional single and combined knockouts, metabolic phenotyping, hepatic transcript analysis

    PMID:22147007

    Open questions at the time
    • Mechanism by which Foxo3 specifically suppresses lipogenic genes independently of Foxo1 not fully delineated
  18. 2016 High

    Endothelial-specific genetic models demonstrated FOXO1 enforces vascular quiescence by repressing MYC, restraining glycolysis and proliferation; MYC re-expression rescued the FOXO1-overexpression phenotype, defining a FOXO1–MYC metabolic antagonism in angiogenesis.

    Evidence Endothelial-specific knockout and overexpression mice, metabolic flux assays, MYC epistasis rescue

    PMID:26735015

    Open questions at the time
    • Whether FOXO1 directly represses MYC transcription or acts post-transcriptionally not resolved
  19. 2017 High

    Identification of SCP4 as the phosphatase that directly dephosphorylates FOXO1 to retain it in the nucleus provided the missing counter-regulatory enzyme to Akt; SCP4-null mice exhibit neonatal hypoglycemia, validating the axis in vivo.

    Evidence In vitro dephosphorylation assay, SCP4 knockout mice, hepatic glucose production assays

    PMID:28851713

    Open questions at the time
    • Regulation of SCP4 itself under fasting/feeding transitions not characterized
  20. 2020 High

    FOXO1 was shown to directly bind the KLF5 promoter in cardiomyocytes, initiating a KLF5→NOX4→ROS→ceramide cascade underlying diabetic cardiomyopathy; cardiomyocyte-specific FOXO1 deletion was protective.

    Evidence ChIP (FOXO1 on KLF5 promoter), cardiomyocyte-specific knockout, AAV rescue, oxidative stress measurements

    PMID:33539225

    Open questions at the time
    • Whether FOXO1-KLF5 axis operates in non-diabetic cardiac stress unknown
  21. 2022 High

    Myeloid-specific FOXO1 deletion revealed its role in promoting M1 macrophage polarization by opposing Stat6 signaling, connecting FOXO1 to inflammatory hepatic pathology in NASH.

    Evidence Myeloid-specific Foxo1 conditional knockout (LysM-Cre), M1/M2 markers, Stat6 pathway analysis, NASH/HFD models

    PMID:35700043

    Open questions at the time
    • Molecular mechanism of FOXO1–Stat6 antagonism (direct binding vs. transcriptional) not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how tissue-specific cofactor assemblies select distinct FOXO1 transcriptional programs, the structural basis for the acetylated-FOXO1–Atg7 autophagy complex, the identity of FOXO1 demethylases and additional deubiquitinases, and how the multiple kinase inputs (Akt, CK1, DYRK1A, NLK, PAK1, cGKI, mTORC2/HDAC) are integrated in real time at the single-cell level.
  • No high-resolution structure of full-length FOXO1 with cofactors
  • Integrative quantitative modeling of multisite post-translational modification crosstalk lacking
  • Tissue-specific FOXO1 interactome not systematically mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 12 GO:0003677 DNA binding 8
Localization
GO:0005634 nucleus 9 GO:0005829 cytosol 4
Pathway
R-HSA-74160 Gene expression (Transcription) 8 R-HSA-162582 Signal Transduction 7 R-HSA-1430728 Metabolism 5 R-HSA-5357801 Programmed Cell Death 5 R-HSA-168256 Immune System 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-9612973 Autophagy 3 R-HSA-1640170 Cell Cycle 1
Partners
AKT1ATG7CTNNB1PMLPRMT1SIRT1SIRT2SKP2
Complex memberships
FOXO1-Atg7FOXO1-beta-cateninPML-SIRT1-FOXO1

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Akt (protein kinase B) directly phosphorylates FOXO1 (FKHR) in vitro and in vivo at three sites (Thr-24, Ser-256, Ser-319), leading to suppression of FOXO1-mediated transcriptional activation; mutation of all three sites to alanine renders FOXO1 resistant to Akt inhibition and causes apoptosis in a DNA-binding-dependent manner. In vitro kinase assay, co-transfection with active/inactive Akt, alanine-substitution mutagenesis, reporter gene assays, apoptosis assay The Journal of biological chemistry High 10358014 10358075
1999 FOXO1 binds in vitro to the insulin-responsive sequence (IRS) in the IGFBP-1 promoter and activates transcription from IRS-containing reporter plasmids; Akt-mediated phosphorylation inhibits this transcriptional activity. In vitro DNA binding assay, luciferase reporter assay, co-transfection The Journal of biological chemistry High 10358014 10358075
2001 FOXO1 confers insulin sensitivity onto glucose-6-phosphatase (G6P) expression in kidney epithelial cells; adenoviral transduction of FOXO1 restores insulin-mediated suppression of dexamethasone/cAMP-induced G6P expression, and dominant-negative FOXO1 partially inhibits G6P and PEPCK expression in primary hepatocytes, establishing FOXO1 as a mediator of insulin regulation of gluconeogenic gene expression. Adenoviral transduction, dominant-negative mutant expression, primary hepatocyte cultures, gene expression analysis The Journal of clinical investigation High 11696581
2001 DYRK1A phosphorylates FOXO1 (FKHR) specifically at Ser-329 in vitro; this phosphorylation reduces FOXO1 nuclear abundance and transcriptional activity; DYRK1A and FOXO1 co-localize in discrete nuclear regions and can be co-immunoprecipitated, suggesting DYRK1A phosphorylates FOXO1 at Ser-329 in vivo. Purification of kinase from skeletal muscle, in vitro kinase assay, co-immunoprecipitation, nuclear co-localization, site-directed mutagenesis, reporter assay The Biochemical journal High 11311120
2002 FOXO1-mediated inhibition of cell cycle progression and transformation requires transcriptional repression of D-type cyclins (Class III targets) rather than activation of insulin-response-sequence genes; chromatin immunoprecipitation confirmed direct FOXO1 occupancy at cyclin D promoters. Transcriptional profiling, chromatin immunoprecipitation (ChIP), functional cell-cycle and transformation assays Cancer cell High 12150827
2003 Insulin-induced Akt-mediated phosphorylation of FOXO1 targets it for ubiquitination and proteasomal degradation; efficient ubiquitination requires both phosphorylation at the PKB consensus sites and cytoplasmic retention, establishing a two-step negative regulation (nuclear exclusion then proteasomal degradation). Proteasome inhibitor treatment, in vivo and in vitro ubiquitination assays, PI3K pathway inhibitors, phosphorylation-site mutants Proceedings of the National Academy of Sciences of the United States of America High 13679577
2003 The androgen receptor (AR) directly interacts with FOXO1 through protein-protein interaction (carboxyl terminus of FOXO1, aa 350–655, with AR A/B region and ligand-binding domain), blocking FOXO1 DNA-binding activity and its ability to induce Fas ligand expression and apoptosis in an AKT-independent manner. In vivo and in vitro co-precipitation, domain-mapping, reporter gene assay, apoptosis/cell-cycle assays Molecular and cellular biology High 12482965
2004 CK1 phosphorylates FOXO1a at Ser-322 and Ser-325 within a multisite phosphorylation domain in vivo; pharmacological inhibition of CK1 with D4476 specifically blocks these phosphorylations and attenuates IGF-1/insulin-induced nuclear exclusion of FOXO1a. Cell-permeable CK1 inhibitor (D4476), phospho-specific analysis, nuclear/cytoplasmic fractionation, H4IIE hepatoma cells EMBO reports High 14710188
2004 Foxo1 is essential for normal vascular development; Foxo1-deficient mice die at embryonic day ~11 with severe defects in angiogenesis, and Foxo1-null endothelial cells derived from ES cells show aberrant morphological response to VEGF, indicating Foxo1 is required for proper endothelial cell response to VEGF signaling. Foxo1 knockout mice (embryonic lethal phenotype), ES-cell-derived endothelial cell differentiation assay, VEGF stimulation The Journal of biological chemistry High 15184386
2004 SIRT1 (Sir2) binds and deacetylates FOXO1 at lysine residues (K242, K245, K262) that are acetylated by CBP, reversing the attenuation of FOXO1 transcriptional activity; SIRT1 is recruited to FOXO1 target promoters (MnSOD, p27kip1) and enhances their expression in a deacetylase-activity-dependent manner. Co-immunoprecipitation, in vitro deacetylation assay, ChIP, reporter assay, deacetylase-inactive mutants Proceedings of the National Academy of Sciences of the United States of America High 15220471
2004 Foxo transcription factors (including Foxo1) drive atrogin-1/MAFbx ubiquitin ligase expression in skeletal muscle; constitutively active Foxo3 acts on the atrogin-1 promoter to cause transcription and dramatic muscle atrophy; dominant-negative Foxo or RNAi-mediated knockdown prevents atrogin-1 induction and muscle atrophy in vitro and in vivo. Constitutively active Foxo constructs, dominant-negative constructs, RNAi in mouse muscle in vivo, promoter reporter assay, myotube atrophy assay Cell High 15109499
2005 FoxO1 protects pancreatic beta cells against oxidative stress by forming a complex with PML and SIRT1 to activate NeuroD and MafA transcription; acetylation of FoxO1 targets it to PML and prevents ubiquitin-dependent degradation, and constitutively nuclear FoxO1 in beta cells prevents hyperglycemia-induced suppression of MafA. Co-immunoprecipitation (FoxO1-PML-SIRT1 complex), acetylation-defective and acetylation-mimicking mutants, transgenic mice, in vivo MafA expression analysis Cell metabolism High 16154098
2005 Acetylation of FOXO1 by CBP at Lys-242, Lys-245, and Lys-262 reduces its DNA-binding affinity by neutralizing positive charges required for DNA interaction; additionally, acetylation increases susceptibility of FOXO1 to Akt-mediated phosphorylation at Ser-253, and DNA binding inhibits PKB phosphorylation of FOXO1 in vitro. In vitro DNA binding assays, in vitro kinase assays, acetylation-mimicking and acetylation-deficient mutants, phosphorylation analysis Proceedings of the National Academy of Sciences of the United States of America High 16076959
2005 Skp2, an oncogenic F-box protein, interacts with and ubiquitinates FOXO1 in an Akt phosphorylation (Ser-256)-dependent manner, promoting FOXO1 proteasomal degradation and abolishing its growth-inhibitory and pro-apoptotic functions. Co-immunoprecipitation, in vitro ubiquitination assay, phosphorylation-site mutants, cell proliferation/survival assays, mouse lymphoma model Proceedings of the National Academy of Sciences of the United States of America High 15668399
2005 Foxo1 (and Foxo3a) overexpression inhibits endothelial cell migration and tube formation; Foxo1 specifically represses angiopoietin-2 expression and binds to the eNOS promoter to repress eNOS expression, establishing Foxo1 as a regulator of angiogenesis-related gene expression in endothelial cells. Constitutively active Foxo constructs, siRNA knockdown, gene expression profiling, ChIP on eNOS promoter, migration/tube formation assays The Journal of clinical investigation High 16100571
2005 PAK1 (p21-activated kinase 1) directly interacts with FOXO1 (FKHR) and phosphorylates it in response to estrogen stimulation, causing perinuclear cytoplasmic retention and preventing FOXO1 from activating Fas ligand promoter transcription; dominant-negative PAK1 restores FOXO1 transcriptional activity. Co-immunoprecipitation, in vitro kinase assay (PAK1 phosphorylating FKHR), localization microscopy, reporter gene assay FEBS letters Medium 12560069
2005 Beta-catenin directly binds FOXO transcription factors and enhances FOXO transcriptional activity in mammalian cells; this interaction is evolutionarily conserved (C. elegans BAR-1/DAF-16) and is enhanced under oxidative stress, establishing beta-catenin as a co-activator of FOXO-dependent stress response. Co-immunoprecipitation, reporter assay, C. elegans genetic epistasis, oxidative stress experiments Science High 15905404
2005 FoxO1a directly activates transcription of the cyclic GMP-dependent protein kinase I (cGKI) gene; the resulting cGKI then phosphorylates FoxO1a and abolishes its DNA-binding activity, establishing an autoregulatory feedback loop that controls myoblast fusion. Reporter gene assay, phosphorylation assay (cGKI on FoxO1a), myoblast fusion assay Molecular and cellular biology Medium 16107711
2006 Constitutively active FoxO1 in transgenic mouse liver increases gluconeogenic gene expression (PEPCK, G6Pase), suppresses glycolytic, pentose phosphate shunt, and lipogenic genes (including glucokinase and SREBP-1c), and impairs glucose tolerance; adenoviral FoxO1 in hepatocytes confirms direct regulation of these metabolic gene programs. Transgenic mice with liver-specific constitutively active FoxO1, gene array, adenoviral transduction of hepatocytes, metabolic phenotyping The Journal of biological chemistry High 16492665
2006 FOXO1A cooperates with HoxA-10 to regulate decidual IGFBP-1 expression; co-immunoprecipitation and ChIP demonstrate physical association of FOXO1A with HoxA-11 and binding of both to the decidual prolactin promoter enhancer, forming a decidual-specific transcriptional complex that switches HoxA-11 from repressor to activator. Co-immunoprecipitation, ChIP, reporter gene assay, siRNA knockdown PloS one Medium 19727442
2008 PRMT1 methylates FOXO1 at Arg-248 and Arg-250 within the Akt phosphorylation consensus motif; this arginine methylation directly blocks Akt-mediated phosphorylation of FOXO1 at Ser-253 in vitro and in vivo, preventing nuclear exclusion and proteasomal degradation, thereby promoting oxidative-stress-induced apoptosis. In vitro methylation assay, in vitro kinase assay, PRMT1 siRNA knockdown, polyubiquitination assay, apoptosis assay, phosphorylation-deficient mutants Molecular cell High 18951090
2008 PGC-1alpha cooperates with FoxO1a and HNF-4alpha to drive selenoprotein P (SeP) promoter activity; PGC-1alpha enhances FoxO1a-stimulated SeP transcription through a FoxO-responsive element; insulin suppresses this axis, establishing FoxO1a as a component of the PGC-1alpha-regulated selenium homeostasis network. Reporter assay, promoter mutagenesis, adenoviral overexpression, primary rat hepatocytes, mRNA/protein analysis Hepatology Medium 18972406
2010 FoxO1 promotes inflammation by enhancing TLR4-mediated signaling in macrophages; ChIP-Seq shows FoxO1 binds multiple enhancer-like elements within the Tlr4 gene and TLR4 pathway genes; TLR4 activation induces Akt which inactivates FoxO1, establishing a self-limiting inflammatory feedback loop. ChIP combined with massively parallel sequencing (ChIP-Seq), FoxO1 knockout macrophages, reporter assay, inflammatory cytokine measurements The EMBO journal High 21045807
2010 TAK1-NLK (Nemo-like kinase) pathway phosphorylates FOXO1 at Pro-directed Ser/Thr residues in the transactivation domain; this phosphorylation inhibits FOXO1 transcriptional activity and causes nuclear exclusion independently of PI3K/Akt; NLK binds FOXO1 and this interaction is evolutionarily conserved in Drosophila. Co-immunoprecipitation, kinase assay (NLK on FOXO1), nuclear/cytoplasmic fractionation, siRNA knockdown of TAK1/NLK, FOXO target gene mRNA assay, PARP cleavage The Journal of biological chemistry Medium 20061393
2010 Cytosolic FoxO1 mediates autophagy independently of its transcriptional activity; in response to oxidative stress or serum starvation, FoxO1 is acetylated by dissociation from SIRT2, and acetylated FoxO1 binds to Atg7 (an E1-like autophagy protein) to induce autophagy and cell death; this is associated with tumor suppressor activity. Co-immunoprecipitation (FoxO1-Atg7 interaction), transcription-deficient FoxO1 mutants, autophagy assays, SIRT2 interaction studies, xenograft tumor model Nature cell biology High 20543840
2011 FoxO1 and SIRT1 regulate beta-cell responses to nitric oxide; FoxO1 translocates from cytoplasm to nucleus in response to nitric oxide and stimulates GADD45α expression for DNA repair; SIRT1 regulates this process—SIRT1 inhibition shifts FoxO1 from a protective (GADD45α/DNA repair) to a proapoptotic (PUMA/caspase-3) program. Nuclear translocation assay, gene expression analysis, SIRT1 pharmacological inhibitors, siRNA, caspase-3 cleavage assay The Journal of biological chemistry Medium 21196578
2011 Hepatic deletion of Foxo1 (but not Foxo3 or Foxo4 alone) reduces blood glucose by decreasing gluconeogenic enzyme gene expression; combined deletion of Foxo1 and Foxo3 additionally increases hepatic lipid synthesis and secretion, demonstrating that Foxo1 specifically controls gluconeogenesis while Foxo3 regulates lipogenic gene expression. Liver-specific Cre/LoxP conditional knockout mice (individual and combined deletions), metabolic phenotyping, liver transcript analysis Endocrinology High 22147007
2013 mTORC2 promotes inactivating phosphorylation of class IIa HDACs, leading to acetylation of FoxO1 (and FoxO3), which releases c-Myc from a suppressive miR-34c network to drive glycolytic reprogramming in glioblastoma; this is an Akt-independent mechanism linking mTORC2 to FoxO acetylation and cancer metabolism. mTORC2 genetic manipulation, HDAC phosphorylation/acetylation assays, FoxO acetylation analysis, c-Myc/miR-34c network analysis, glioblastoma patient samples Cell metabolism High 24140020
2014 FOXO1/3 knockdown in vascular smooth muscle cells phenocopies PTEN deficiency by increasing Runx2 protein via decreased Runx2 ubiquitination, promoting vascular calcification; AKT activation causes FOXO1/3 nuclear exclusion, establishing a PTEN/AKT/FOXO1/3/Runx2 ubiquitination axis controlling VSMC calcification. SMC-specific PTEN knockout mice (Cre/LoxP), siRNA knockdown, in vitro calcification assay, Runx2 ubiquitination assay, ex vivo arterial calcification Arteriosclerosis, thrombosis, and vascular biology Medium 25378413
2015 FOXO1 directly regulates CCR7 and ICAM-1 promoters (shown by ChIP and promoter reporter assays) in dendritic cells; FOXO1 nuclear localization is induced by bacteria via the MAPK pathway; lineage-specific FOXO1 deletion impairs DC phagocytosis, chemotaxis, and lymph node homing, which can be rescued by ICAM-1 and CCR7 re-expression. ChIP, promoter reporter assay, lineage-specific knockout (CD11c.Cre), rescue with plasmid transfection, in vivo lymph node homing assay Journal of immunology High 25786691
2015 FOXO1 enhances keratinocyte migration and wound healing by upregulating TGFβ1 under normal glucose conditions; under high glucose, FOXO1 nuclear localization is induced but FOXO1 does not bind the TGFβ1 promoter—instead it drives SERPINB2 and CCL20 expression that inhibits migration; insulin treatment or FOXO1 silencing rescues impaired migration in high glucose. Lineage-specific Foxo1 deletion, FOXO1 promoter binding analysis, siRNA, high-glucose cell culture, wound healing migration assay The Journal of cell biology High 25918228
2016 FOXO1 suppresses MYC signaling in endothelial cells to restrain glycolysis and mitochondrial respiration, acting as a gatekeeper of endothelial quiescence; endothelial-restricted FOXO1 deletion causes increased EC proliferation and vessel hyperplasia, while forced FOXO1 expression restricts vascular expansion; restoration of MYC in FOXO1-overexpressing endothelium normalizes metabolism and branching. Endothelial-specific knockout and overexpression mouse models, metabolic flux assays (glycolysis, respiration), MYC rescue experiments, EC proliferation assays Nature High 26735015
2017 DDB1-CUL4A E3 ubiquitin ligase promotes FOXO1-driven hepatic gluconeogenesis by degrading CRY1 (a known DDB1 target); loss of Ddb1 in hepatocytes downregulates FOXO1 protein and impairs gluconeogenic response; CRY1 depletion increases nuclear FOXO1 abundance and enhances gluconeogenesis, linking circadian clock protein degradation to FOXO1 stability. Hepatocyte-specific Ddb1 knockout mice, Cry1 depletion in vivo, FOXO1 protein stability analysis, gluconeogenic gene expression, glucose production assay Diabetes Medium 28790135
2017 SCP4 (CTDSPL2) is a nuclear phosphatase that directly dephosphorylates FoxO1/3a, promoting nuclear retention and transcriptional activation of PEPCK1 and G6PC gluconeogenic genes; SCP4 overexpression increases hepatic glucose production; SCP4 gene ablation causes neonatal hypoglycemia. In vitro dephosphorylation assay (SCP4 on FoxO1/3a), ectopic expression, siRNA knockdown, SCP4 knockout mice (neonatal hypoglycemia), glucose production assay Diabetes High 28851713
2018 FOXO1 directly regulates VEGFA expression in keratinocytes (shown by in vitro promoter assay); keratinocyte-specific FOXO1 deletion reduces VEGFA expression in wounds, resulting in reduced endothelial cell proliferation, reduced angiogenesis, and impaired wound re-epithelialization. Keratinocyte-specific Foxo1 knockout mice, VEGFA promoter reporter assay, endothelial proliferation assay, porcine wound model with FOXO1 inhibitor The Journal of pathology High 29574902
2018 Foxo1 directly binds the Il9 and Irf4 promoters in Th9 cells (shown by ChIP and luciferase assays) to transactivate them; pharmacological or genetic disruption of Foxo1 in CD4+ T cells reduces IL-9 and promotes IL-17A/IFNγ; adoptive transfer of Foxo1-inhibitor-treated Th9 cells reduces asthma-like symptoms. ChIP, luciferase promoter assay, Foxo1 pharmacological inhibitor (AS1842856), CD4-specific Foxo1 knockout, adoptive transfer airway allergy model Scientific reports Medium 29339772
2019 Glucagon suppresses hepatic mitochondrial complex III and IV activity and reduces mitochondrial biogenesis (NRF1, TFAM, MFN2 expression) in a FOXO1-dependent manner; hepatocyte-specific Foxo1 deletion largely rescues glucagon-induced mitochondrial dysfunction, establishing FOXO1 as a mediator of glucagon's effects on mitochondrial function. Foxo1 hepatocyte-specific knockout mice, glucagon treatment, mitochondrial function assays (complex activity), db/db diabetic mice The Journal of endocrinology Medium 31026811
2020 METTL14 promotes FOXO1 expression in endothelial cells by directly binding FOXO1 mRNA, increasing its m6A modification, and enhancing translation through YTHDF1 recognition; METTL14 also interacts with FOXO1 protein and together they act on VCAM-1 and ICAM-1 promoters to promote inflammatory gene transcription. Methylated RNA immunoprecipitation (RIP) sequencing, RIP assay, co-immunoprecipitation, ChIP, METTL14 knockout mice, TNF-α inflammation model Theranostics Medium 32802173
2020 FOXO1 binds directly to the KLF5 promoter in cardiomyocytes to increase KLF5 expression; KLF5 in turn binds the NOX4 promoter to induce NOX4 expression, reactive oxygen species, and ceramide accumulation, causing diabetic cardiomyopathy; cardiomyocyte-specific FOXO1 deletion protects from diabetic cardiomyopathy by reducing KLF5. ChIP (FOXO1 on KLF5 promoter; KLF5 on NOX4 promoter), cardiomyocyte-specific FOXO1 knockout mice, AAV-mediated KLF5 delivery, pharmacological KLF5 inhibition, oxidative stress and ceramide measurements Circulation research High 33539225
2020 S100A11 interacts with HDAC6 to inhibit HDAC6 deacetylase activity, thereby releasing FOXO1 from HDAC6 binding and increasing FOXO1 acetylation; acetylated FOXO1 activates autophagy and lipogenesis programs promoting liver steatosis. Co-immunoprecipitation (S100A11-HDAC6 interaction), HDAC6 inhibitor, FOXO1 inhibitor, adenoviral overexpression, in vivo high-fat diet model, lipid staining Cellular and molecular gastroenterology and hepatology Medium 33075563
2021 Akt phosphorylation of FoxO1 is required for Sox10 expression in oligodendrocytes; unphosphorylated (nuclear) FoxO1 represses the Sox10 promoter; Akt-triple-knockout oligodendrocyte lineage mice lack mature oligodendrocytes and myelination with downregulated Sox10, identifying a FoxO1 phosphorylation-dependent mechanism for oligodendrocyte differentiation. OL lineage-specific Akt1/2/3 triple conditional knockout mice, Sox10 promoter reporter assay, FoxO1 phosphorylation-site mutants, ChIP (FoxO1 on Sox10 promoter) The Journal of neuroscience Medium 34385359
2021 Foxo1 in intestinal epithelial cells regulates goblet cell autophagy and mucus secretion; IEC-specific Foxo1 deletion impairs goblet cell autophagy and mucus secretion, leading to gut microbiota dysbiosis, disrupted tight junction organization, and increased susceptibility to intestinal inflammation. Intestinal epithelial cell-specific Foxo1 conditional knockout mice, goblet cell autophagy assays, microbiome analysis, tight junction protein analysis, colitis susceptibility assay The Journal of experimental medicine Medium 34287641
2022 FoxO1 in hepatic macrophages (Kupffer cells) promotes pro-inflammatory M1 polarization by counteracting Stat6 signaling; myeloid-specific FoxO1 knockout skews macrophage polarization from M1 to M2 and reduces hepatic inflammation, steatosis, and fibrosis in NASH. Myeloid-specific FoxO1 conditional knockout (LysM-Cre), M1/M2 polarization markers, Stat6 pathway analysis, NASH diet model, high-fat diet model The Journal of clinical investigation High 35700043
2023 FOXO1 directly binds the promoter regions of CD36 and STEAP4 genes in bovine adipocytes (shown by ChIP and site-directed mutagenesis) and regulates their transcriptional activity, linking FOXO1 to lipogenesis through the AMPK and PI3K/AKT pathways. ChIP, site-directed mutagenesis of FOXO1 binding sites, transcriptomic and metabolomics analyses, siRNA knockdown International journal of biological macromolecules Medium 37506793

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell 2402 15109499
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2000 AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1. Nature 1227 10783894
2009 A census of human transcription factors: function, expression and evolution. Nature reviews. Genetics 1191 19274049
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2011 Akt, FoxO and regulation of apoptosis. Biochimica et biophysica acta 922 21440011
2004 Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation. Cell 837 15084259
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
1993 Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma. Nature genetics 815 8275086
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1999 Negative regulation of the forkhead transcription factor FKHR by Akt. The Journal of biological chemistry 654 10358014
2005 Functional interaction between beta-catenin and FOXO in oxidative stress signaling. Science (New York, N.Y.) 621 15905404
1999 Phosphorylation of the transcription factor forkhead family member FKHR by protein kinase B. The Journal of biological chemistry 604 10358075
2011 FoxO transcription factors; Regulation by AKT and 14-3-3 proteins. Biochimica et biophysica acta 593 21708191
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2002 PAX3-FKHR and PAX7-FKHR gene fusions are prognostic indicators in alveolar rhabdomyosarcoma: a report from the children's oncology group. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 558 12039929
2010 Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity. Nature cell biology 519 20543840
2004 Silent information regulator 2 potentiates Foxo1-mediated transcription through its deacetylase activity. Proceedings of the National Academy of Sciences of the United States of America 504 15220471
2009 Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells. The Journal of biological chemistry 497 19574223
2001 The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression. The Journal of clinical investigation 495 11696581
2005 FoxO1 protects against pancreatic beta cell failure through NeuroD and MafA induction. Cell metabolism 492 16154098
2016 FOXO1 couples metabolic activity and growth state in the vascular endothelium. Nature 479 26735015
2005 Involvement of Foxo transcription factors in angiogenesis and postnatal neovascularization. The Journal of clinical investigation 456 16100571
2008 DBC1 is a negative regulator of SIRT1. Nature 445 18235501
2005 Skp2 inhibits FOXO1 in tumor suppression through ubiquitin-mediated degradation. Proceedings of the National Academy of Sciences of the United States of America 444 15668399
2003 Insulin-induced phosphorylation of FKHR (Foxo1) targets to proteasomal degradation. Proceedings of the National Academy of Sciences of the United States of America 439 13679577
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2006 FoxO1 regulates multiple metabolic pathways in the liver: effects on gluconeogenic, glycolytic, and lipogenic gene expression. The Journal of biological chemistry 433 16492665
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2005 Acetylation of Foxo1 alters its DNA-binding ability and sensitivity to phosphorylation. Proceedings of the National Academy of Sciences of the United States of America 419 16076959
2008 Arginine methylation of FOXO transcription factors inhibits their phosphorylation by Akt. Molecular cell 378 18951090
2010 Fusion gene-negative alveolar rhabdomyosarcoma is clinically and molecularly indistinguishable from embryonal rhabdomyosarcoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 377 20351326
2006 GCN5 acetyltransferase complex controls glucose metabolism through transcriptional repression of PGC-1alpha. Cell metabolism 372 16753578
2013 mTOR complex 2 controls glycolytic metabolism in glioblastoma through FoxO acetylation and upregulation of c-Myc. Cell metabolism 363 24140020
2002 A novel mechanism of gene regulation and tumor suppression by the transcription factor FKHR. Cancer cell 363 12150827
2017 The regulation of FOXO1 and its role in disease progression. Life sciences 340 29158051
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
1998 Cloning and characterization of three human forkhead genes that comprise an FKHR-like gene subfamily. Genomics 297 9479491
2004 Abnormal angiogenesis in Foxo1 (Fkhr)-deficient mice. The Journal of biological chemistry 284 15184386
2017 PAX3-FOXO1 Establishes Myogenic Super Enhancers and Confers BET Bromodomain Vulnerability. Cancer discovery 258 28446439
2004 D4476, a cell-permeant inhibitor of CK1, suppresses the site-specific phosphorylation and nuclear exclusion of FOXO1a. EMBO reports 227 14710188
2020 METTL14 aggravates endothelial inflammation and atherosclerosis by increasing FOXO1 N6-methyladeosine modifications. Theranostics 224 32802173
2001 The kinase DYRK1A phosphorylates the transcription factor FKHR at Ser329 in vitro, a novel in vivo phosphorylation site. The Biochemical journal 218 11311120
2010 FoxO1 regulates Tlr4 inflammatory pathway signalling in macrophages. The EMBO journal 212 21045807
2004 Pax3:Fkhr interferes with embryonic Pax3 and Pax7 function: implications for alveolar rhabdomyosarcoma cell of origin. Genes & development 196 15520281
1999 The Pax3-FKHR oncoprotein is unresponsive to the Pax3-associated repressor hDaxx. The EMBO journal 183 10393185
2011 Hepatic suppression of Foxo1 and Foxo3 causes hypoglycemia and hyperlipidemia in mice. Endocrinology 146 22147007
2003 AKT-independent protection of prostate cancer cells from apoptosis mediated through complex formation between the androgen receptor and FKHR. Molecular and cellular biology 137 12482965
2008 PAX3-FOXO1 fusion gene in rhabdomyosarcoma. Cancer letters 136 18457914
1996 In vivo amplification of the PAX3-FKHR and PAX7-FKHR fusion genes in alveolar rhabdomyosarcoma. Human molecular genetics 132 8789435
2020 KLF5 Is Induced by FOXO1 and Causes Oxidative Stress and Diabetic Cardiomyopathy. Circulation research 122 33539225
2012 FoxO1 is crucial for sustaining cardiomyocyte metabolism and cell survival. Cardiovascular research 119 23263330
2006 FOXO1A is a candidate for the 13q14 tumor suppressor gene inhibiting androgen receptor signaling in prostate cancer. Cancer research 116 16849544
2019 Mucosal Immunity and the FOXO1 Transcription Factors. Frontiers in immunology 108 31849924
2008 Selenoprotein P expression is controlled through interaction of the coactivator PGC-1alpha with FoxO1a and hepatocyte nuclear factor 4alpha transcription factors. Hepatology (Baltimore, Md.) 104 18972406
1996 The hybrid PAX3-FKHR fusion protein of alveolar rhabdomyosarcoma transforms fibroblasts in culture. Proceedings of the National Academy of Sciences of the United States of America 103 8790412
2014 Inhibition of FOXO1/3 promotes vascular calcification. Arteriosclerosis, thrombosis, and vascular biology 102 25378413
2020 Resveratrol promotes osteogenesis via activating SIRT1/FoxO1 pathway in osteoporosis mice. Life sciences 91 32057903
2014 FOXO1, TGF-β regulation and wound healing. International journal of molecular sciences 89 25226535
2007 Haplotypes in the human Foxo1a and Foxo3a genes; impact on disease and mortality at old age. European journal of human genetics : EJHG 89 17245409
2007 FOXC1 is required for cell viability and resistance to oxidative stress in the eye through the transcriptional regulation of FOXO1A. Human molecular genetics 89 17993506
2003 Estrogen regulation of Pak1 and FKHR pathways in breast cancer cells. FEBS letters 87 12560069
2007 Effects of PAX3-FKHR on malignant phenotypes in alveolar rhabdomyosarcoma. Biochemical and biophysical research communications 85 18022385
2009 HoxA-11 and FOXO1A cooperate to regulate decidual prolactin expression: towards inferring the core transcriptional regulators of decidual genes. PloS one 79 19727442
2006 APPL1, APPL2, Akt2 and FOXO1a interact with FSHR in a potential signaling complex. Molecular and cellular endocrinology 78 17030088
2019 Molecular mechanisms of FOXO1 in adipocyte differentiation. Journal of molecular endocrinology 76 30780132
2015 Functional regulation of FoxO1 in neural stem cell differentiation. Cell death and differentiation 76 26470727
2018 FOXO1 regulates VEGFA expression and promotes angiogenesis in healing wounds. The Journal of pathology 74 29574902
2020 S100A11 Promotes Liver Steatosis via FOXO1-Mediated Autophagy and Lipogenesis. Cellular and molecular gastroenterology and hepatology 72 33075563
2021 FOXO1 constrains activation and regulates senescence in CD8 T cells. Cell reports 69 33503413
1995 The alveolar rhabdomyosarcoma PAX3/FKHR fusion protein is a transcriptional activator. Oncogene 67 7630639
2015 FOXO1 differentially regulates both normal and diabetic wound healing. The Journal of cell biology 66 25918228
2010 FoxO1 - the key for the pathogenesis and therapy of acne? Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG 66 20151947
2006 Forkhead transcription factor FOXO1A is critical for induction of human decidualization. The Journal of endocrinology 66 16614392
2008 Overexpression of phospho-Akt correlates with phosphorylation of EGF receptor, FKHR and BAD in nasopharyngeal carcinoma. Oncology reports 64 18202777
2001 PAX3-FKHR induces morphological change and enhances cellular proliferation and invasion in rhabdomyosarcoma. The American journal of pathology 64 11549601
2011 FoxO1 and SIRT1 regulate beta-cell responses to nitric oxide. The Journal of biological chemistry 62 21196578
2018 PAR2 promotes M1 macrophage polarization and inflammation via FOXO1 pathway. Journal of cellular biochemistry 59 30552714
2012 The yeast forkhead transcription factors fkh1 and fkh2 regulate lifespan and stress response together with the anaphase-promoting complex. PLoS genetics 59 22438832
2012 Alveolar rhabdomyosarcoma-associated proteins PAX3/FOXO1A and PAX7/FOXO1A suppress the transcriptional activity of MyoD-target genes in muscle stem cells. Oncogene 58 22710712
2002 Identification of target genes regulated by PAX3 and PAX3-FKHR in embryogenesis and alveolar rhabdomyosarcoma. Genomics 57 11863357
2022 HB-EGF induces mitochondrial dysfunction via estrogen hypersecretion in granulosa cells dependent on cAMP-PKA-JNK/ERK-Ca2+-FOXO1 pathway. International journal of biological sciences 56 35342363
2020 Adipose Tissue and FoxO1: Bridging Physiology and Mechanisms. Cells 56 32244542
2021 Foxo1 controls gut homeostasis and commensalism by regulating mucus secretion. The Journal of experimental medicine 53 34287641
2018 Maintenance of CD4 T cell fitness through regulation of Foxo1. Nature immunology 53 29988091
2022 Myeloid FoxO1 depletion attenuates hepatic inflammation and prevents nonalcoholic steatohepatitis. The Journal of clinical investigation 52 35700043
2012 Regulation of budding yeast mating-type switching donor preference by the FHA domain of Fkh1. PLoS genetics 52 22496671
2007 The PAX3-FKHR fusion gene of rhabdomyosarcoma cooperates with loss of p16INK4A to promote bypass of cellular senescence. Cancer research 52 17638879
2006 Gluconeogenesis: re-evaluating the FOXO1-PGC-1alpha connection. Nature 51 17024043
1995 Structural characterization of the FKHR gene and its rearrangement in alveolar rhabdomyosarcoma. Human molecular genetics 51 8634710
2015 FOXO1 regulates dendritic cell activity through ICAM-1 and CCR7. Journal of immunology (Baltimore, Md. : 1950) 50 25786691
2017 SAPHO, autophagy, IL-1, FoxO1, and Propionibacterium (Cutibacterium) acnes. Joint bone spine 48 28499891
2016 FoxO1 antagonist suppresses autophagy and lipid droplet growth in adipocytes. Cell cycle (Georgetown, Tex.) 47 27260854
1996 Novel formation and amplification of the PAX7-FKHR fusion gene in a case of alveolar rhabdomyosarcoma. Genes, chromosomes & cancer 46 8889501
2010 Regulation of FOXO1 by TAK1-Nemo-like kinase pathway. The Journal of biological chemistry 45 20061393
2014 Down Regulation of FOXO1 Promotes Cell Proliferation in Cervical Cancer. Journal of Cancer 44 25157276
2010 Foxo1 regulates marginal zone B-cell development. European journal of immunology 42 20449867
2005 Coordinated oncogenic transformation and inhibition of host immune responses by the PAX3-FKHR fusion oncoprotein. The Journal of experimental medicine 41 16287709
2002 Effect of multiple phosphorylation events on the transcription factors FKHR, FKHRL1 and AFX. Biochemical Society transactions 41 12196101
2002 Saccharomyces forkhead protein Fkh1 regulates donor preference during mating-type switching through the recombination enhancer. Genes & development 40 12183363
2016 Quantitative BrdU immunoprecipitation method demonstrates that Fkh1 and Fkh2 are rate-limiting activators of replication origins that reprogram replication timing in G1 phase. Genome research 38 26728715
2012 Carnitine palmitoyltransferase 1A (CPT1A): a transcriptional target of PAX3-FKHR and mediates PAX3-FKHR-dependent motility in alveolar rhabdomyosarcoma cells. BMC cancer 37 22533991
2020 The role and molecular mechanism of FoxO1 in mediating cardiac hypertrophy. ESC heart failure 35 33089967
2022 Targeting KDM4 for treating PAX3-FOXO1-driven alveolar rhabdomyosarcoma. Science translational medicine 34 35857643
2016 HDAC2 regulates FoxO1 during RANKL-induced osteoclastogenesis. American journal of physiology. Cell physiology 34 26962001
2005 Regulation of the proapoptotic factor FOXO1 (FKHR) in cardiomyocytes by growth factors and alpha1-adrenergic agonists. Endocrinology 34 16020479
2016 Aquaporin 9 inhibits hepatocellular carcinoma through up-regulating FOXO1 expression. Oncotarget 33 27329843
2016 PAX3-FOXO1A Expression in Rhabdomyosarcoma Is Driven by the Targetable Nuclear Receptor NR4A1. Cancer research 31 27864345
2015 FOXO1 mediates RANKL-induced osteoclast formation and activity. Journal of immunology (Baltimore, Md. : 1950) 31 25694609
2023 FOXO1 regulates the formation of bovine fat by targeting CD36 and STEAP4. International journal of biological macromolecules 30 37506793
2018 Foxo1 Promotes Th9 Cell Differentiation and Airway Allergy. Scientific reports 30 29339772
2012 P-cadherin is a direct PAX3-FOXO1A target involved in alveolar rhabdomyosarcoma aggressiveness. Oncogene 30 22710718
2021 Galanin promotes autophagy and alleviates apoptosis in the hypertrophied heart through FoxO1 pathway. Redox biology 29 33493902
2019 Glucagon regulates hepatic mitochondrial function and biogenesis through FOXO1. The Journal of endocrinology 29 31026811
2018 Trichostatin A activates FOXO1 and induces autophagy in osteosarcoma. Archives of medical science : AMS 29 30697272
2007 PAX3 and PAX3-FKHR promote rhabdomyosarcoma cell survival through downregulation of PTEN. Cancer letters 29 17350164
2021 Akt Regulates Sox10 Expression to Control Oligodendrocyte Differentiation via Phosphorylating FoxO1. The Journal of neuroscience : the official journal of the Society for Neuroscience 28 34385359
2021 TGFβ1 signaling protects chondrocytes against oxidative stress via FOXO1-autophagy axis. Osteoarthritis and cartilage 28 34419603
2023 Suppression of FOXO1 attenuates inflamm-aging and improves liver function during aging. Aging cell 27 37602516
2017 DDB1-Mediated CRY1 Degradation Promotes FOXO1-Driven Gluconeogenesis in Liver. Diabetes 27 28790135
2005 FoxO1a-cyclic GMP-dependent kinase I interactions orchestrate myoblast fusion. Molecular and cellular biology 27 16107711
2018 FoxO1 enhances differentiation and apoptosis in human primary keratinocytes. Experimental dermatology 26 30144329
2021 FOXF1 is required for the oncogenic properties of PAX3-FOXO1 in rhabdomyosarcoma. Oncogene 25 33627785
2009 Atrial natriuretic peptide promotes pancreatic islet beta-cell growth and Akt/Foxo1a/cyclin D2 signaling. Endocrinology 25 19837876
2008 Tissue expression of porcine FoxO1 and its negative regulation during primary preadipocyte differentiation. Molecular biology reports 25 18293098
2017 SCP4 Promotes Gluconeogenesis Through FoxO1/3a Dephosphorylation. Diabetes 24 28851713
2009 Localisation and expression of FoxO1 proteins in human gestational tissues. Placenta 23 19150739
2007 CDK2 and FOXO1: a fork in the road for cell fate decisions. Cell cycle (Georgetown, Tex.) 23 17457058
2012 AKT and PAX3-FKHR cooperation enforces myogenic differentiation blockade in alveolar rhabdomyosarcoma cell. Cell cycle (Georgetown, Tex.) 22 22333587