Property Summary

NCBI Gene PubMed Count 85
PubMed Score 252.73
PubTator Score 76.82

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (3)

Disease Target Count P-value
juvenile dermatomyositis 1189 3.0e-09
osteosarcoma 7933 9.0e-09
psoriasis 6685 1.2e-05
medulloblastoma, large-cell 6234 3.4e-05
adult high grade glioma 2148 1.6e-04
lung cancer 4473 4.3e-02
Disease Target Count Z-score Confidence
Cancer 2346 4.115 2.1
Disease Target Count Z-score Confidence
Cutaneous fibrous histiocytoma 16 4.78 2.4

Expression

  Differential Expression (6)

Disease log2 FC p
psoriasis -2.700 1.2e-05
osteosarcoma -3.746 9.0e-09
medulloblastoma, large-cell -1.400 3.4e-05
juvenile dermatomyositis -1.034 3.0e-09
lung cancer -1.300 4.3e-02
adult high grade glioma -1.100 1.6e-04

Gene RIF (62)

PMID Text
26715362 The data demonstrated that elevated miR-150 targets FOXO4 expression and therefore regulates multiple genes expression, resulting in cervical cancer cell growth and survival.
26463624 miR-664 functions as an oncogene miRNA and has an important role in promoting human osteosarcoma cell proliferation by suppressing FOXO4 expression.
25958948 Porphyromonas gingivalis-induced reactive oxygen species activate FOXO transcription factors through JNK signalling, and that FOXO1 controls oxidative stress responses, inflammatory cytokine production and cell survival.
25753202 study demonstrated that miR-1274a prompted gastric cancer cells growth and migration through dampening FOXO4 expression thus provided a potential target for human gastric cancer therapy
25648147 FOXOs support the metabolic requirements of normal and tumor cells by promoting IDH1 expression.
25053419 Data indicate that glycogen synthase kinase 3 beta (GSK3beta) and transcription factors FOXO1/3/4 promote hepatoma cell proliferation through type I insulin-like growth factor receptor (IGF-IR).
25007147 Case Report: CIC-FOXO4 fusion sarcoma is a new type of Ewing-like sarcoma that has a specific genetic signature.
24984152 results demonstrate that HKa accelerates the onset of EPC senescence by stimulating JNK/FOXO4/MnSOD pathway, its effect is mediated by the HC
24983969 data strongly suggest that increased PI3K/AKT-mediated metastatic invasiveness in CaP is associated with FOXO4 loss, and that mechanisms to induce FOXO4 re-expression might suppress CaP metastatic aggressiveness.
24935588 Cox regression analysis indicated FoxO4 to be an independent prognostic factor in non-small cell lung cancers and suggested that FoxO4 might inhibit the process of EMT in non-small cell lung cancers, and might therefore be a target for therapy.
24886657 Our data suggest that loss of FOXO4 expression contributes to gastric cancer growth and metastasis, and it may serve as a potential therapeutic target for gastric cancer.
24663349 FOXO4KD-EPCs injected into the rat ischemic limb brought less apoptosis and more neovascularization than EPCs
24353279 Data show that forkhead transcription factor 4 (FoxO4) interacts with sterol regulatory element binding protein (SREBP)2 and hypoxia inducible factor (HIF)2alpha to modulate lanosterol 14alpha demethylase (CYP51) promoter activity.
23770673 Data show that small GTPase RALA regulates formation of a JIP1 (C-Jun-amino-terminal-interacting protein 1) scaffold complex to propagate JNK signaling toward FOXO4 (forkhead box O transcription factor) in response to reactive oxygen species (ROS).
23707940 Taken together, our findings not only suggest that miR-421 promotes nasopharyngeal carcinoma cell proliferation and anti-apoptosis, but also uncover a novel regulatory mechanism for inactivation of FOXO4 in nasopharyngeal carcinoma.
23551888 We find that loss of FOXO4 reduces the potential of hESCs to differentiate into neural lineages.
23333309 Disulfide formation with transportin-1 is required for nuclear localization and the activation of FOXO4 induced by reactive oxygen species.
22411791 Inhibition of endogenous FOXO proteins attenuated tetradecanoylphorbol Acetate/PDGF-BB mediated differentiation of neuroblastoma cells.
22285440 Coding mutations within the FOXO4 gene are not associated with premature ovarian failure in women from the Tunisian population.
22125836 FOXO4 may function as a tumor suppressor in the development and progression of colorectal cancer.
22112832 Data suggest that expression of cytoplasmic FoxO4 in placenta, fetal membranes, and decidua is altered by parturition/labor, preterm chorioamnionitis, and pro-inflammatory stimuli; silencing of FoxO4 gene initiates apoptosis in placental cell lines.
21934092 identified FOXO4 and PDCD4 as direct and functional targets of miR-499-5p
21708191 Studies indictet that the mammalian FoxO family consists of FoxO1, 3, 4 and 6 and are regulated by by AKT and 14-3-3 proteins.
21613825 Studies indicate that FoxO1, 3 and 4 genes were discovered at the chromosomal breakpoints found in cancers and were initially implicated in cancer.
21567078 Foxo4 may be a useful target for suppression in the treatment of HBV-associated hepatocellular carcinoma cells.
21536589 Findings support that ATXN3 plays an important role in regulating the FOXO4-dependent antioxidant stress response via SOD2.
21525355 Tax induces a dose-dependent degradation of FoxO4 by the ubiquitin-proteasome pathway.
21510935 DEPP is regulated at the level of transcription by FoxO in human vascular endothelial cells
21454807 demonstrated that adiponectin activated 5'-AMP-activated protein kinase alpha2 isoform, leading to inhibition of mammalian target of rapamycin complex 1 and S6K1. This in turn stabilized insulin receptor substrate-1, driving Akt2-mediated inhibition of FoxO4
21388494 gene study of FOXO4, reveals no association with human longevity in Germans
21123876 structure of the FOXO4-DNA-binding domain (DBD)-DNA complex suggests that both direct water-DNA base contacts and the unique water-network interactions contribute to FOXO-DBD binding to the DNA in a sequence-specific manner
20934750 greater in fetal membranes obtained from the supracervical compared to distal site
20570964 a conserved critical Ku70 role for FOXO function toward coordination of a survival program
20348951 PKG inhibits TCF signaling in colon cancer cells by blocking beta-catenin expression and activating FOXO4.
20136501 Findings show that oxidative stress and FOXO4 induce PAI-1 expression through modulation of HIF-1alpha and CREB protein levels and that enhanced CREB binding to the PAI-1 promoter is critical for the PAI-1 induction under oxidative stress.
20037138 FoxO4 acts on CYP51 to regulate the late steps of cholesterol biosynthesis.
19932102 these data provide a mechanism of FOXO4 anti-oxidative protection through O-GlcNAcylation.
19560465 FoxO4 is down-regulated in patients with inflammatory bowel disease.
19416966 The model of the complex suggests that the forkhead domain of FOXO4 is docked within the central channel of the 14-3-3 protein dimer, consistent with the hypothesis that 14-3-3 masks the DNA binding interface of FOXO4.
19244250 Results suggest that the expression of FOXO1 and FOXO4 genes is stimulated by FOXO3 and possibly by other FOXO factors in a positive feedback loop, which is disrupted by growth factors.
18794148 Pin1 is identified as a novel negative FOXO regulator, interconnecting FOXO phosphorylation and monoubiquitination in response to cellular stress to regulate p27(kip1).
18692812 FOXO1, FOXO3, and FOXO4 are expressed in human luteinized mural granulosa cells, which may suggest that these transcription factors are also involved in human folliculogenesis and luteinization.
18665269 Mdm2 induces mono-ubiquitination of FOXO4
18648506 AFX splice variants exhibit dominant negative activity and inhibit AFXalpha-mediated tumor cell apoptosis
17244620 both N- and C-terminal regions of forkhead domain are important for stability of the FoxO4-DBD.DNA complex
16571842 Observational study of gene-disease association. (HuGE Navigator)
16215946 The patients with immunophenotype of Pre-B-acute lymphoblastic leukemia were found to carry: MLL/AFX.
16114898 DNA-binding domain of FoxO4 remains relatively mobile while bound to the 14-3-3 protein.
15905404 results demonstrate a role for beta-catenin in regulating FOXO function that is particularly important under conditions of oxidative stress
15824087 results show that Forkhead transcription factor 4-dependent expression of Bim protein plays a pivotal role for endothelial progenitor cell apoptosis
15688030 FOXO4 gene as a novel anticancer agent for HER2-overexpressing cells.
15688004 Introduction of dominant-negative FoxO into mousse cells partially rescues cAMP-induced inhibition of proliferation.
15538382 Data show that low levels of oxidative stress generated by treatment with hydrogen peroxide induce the activation of FOXO4.
15126506 Data demonstrate that acetylation functions in a second pathway of negative control for FOXO factors and provides a novel mechanism whereby hSir2(SIRT1) can promote cellular survival and increase lifespan.
14690436 Phosphorylation of FOXO4 by protein kinase B on threonine-28 and serine-193 leads to a tight association of FOXO4 with 14-3-3 zeta, causing complete inhibition of DNA binding, most likely by masking of the DNA binding surface of Forkhead domain by 14-3-3.
12964026 CBP-induced acetylation of AFX is a novel modification mechanism by which AFX keeps the transcriptional activity mitigating in the nucleus
12960271 fMLP-stimulated neutrophils coordinate the regulation of FOXO transcription factors and the survival factor Mcl-1, a mechanism that may allow neutrophils to alter their survival.
12761217 FOXO4 induces the down-regulation of hypoxia-inducible factor 1 alpha by a von Hippel-Lindau protein-independent mechanism
12192052 the MLL-AFX fusion protein requires the transcriptional effector domains of AFX to transform myeloid progenitors and interfere with forkhead protein function
11884591 Control of cell cycle exit and entry by protein kinase B-regulated forkhead transcription factors
11779849 AFX zeta is a downstream target of both the phosphatidylinositol 3-kinase/PKB insulin signaling pathway and an AMP-activated protein kinase-dependent pathway.
11777915 The forkhead transcription factor AFX activates apoptosis by induction of the BCL-6 transcriptional repressor.

AA Sequence

MDPGNENSATEAAAIIDLDPDFEPQSRPRSCTWPLPRPEIANQPSEPPEVEPDLGEKVHTEGRSEPILLP      1 - 70
SRLPEPAGGPQPGILGAVTGPRKGGSRRNAWGNQSYAELISQAIESAPEKRLTLAQIYEWMVRTVPYFKD     71 - 140
KGDSNSSAGWKNSIRHNLSLHSKFIKVHNEATGKSSWWMLNPEGGKSGKAPRRRAASMDSSSKLLRGRSK    141 - 210
APKKKPSVLPAPPEGATPTSPVGHFAKWSGSPCSRNREEADMWTTFRPRSSSNASSVSTRLSPLRPESEV    211 - 280
LAEEIPASVSSYAGGVPPTLNEGLELLDGLNLTSSHSLLSRSGLSGFSLQHPGVTGPLHTYSSSLFSPAE    281 - 350
GPLSAGEGCFSSSQALEALLTSDTPPPPADVLMTQVDPILSQAPTLLLLGGLPSSSKLATGVGLCPKPLE    351 - 420
APGPSSLVPTLSMIAPPPVMASAPIPKALGTPVLTPPTEAASQDRMPQDLDLDMYMENLECDMDNIISDL    421 - 490
MDEGEGLDFNFEPDP                                                           491 - 505
//

Text Mined References (88)

PMID Year Title
26715362 2015 microRNA-150 promotes cervical cancer cell growth and survival by targeting FOXO4.
26463624 2015 Mir-664 promotes osteosarcoma cells proliferation via downregulating of FOXO4.
25958948 2015 FOXO responses to Porphyromonas gingivalis in epithelial cells.
25753202 2015 The role of microRNA-1274a in the tumorigenesis of gastric cancer: accelerating cancer cell proliferation and migration via directly targeting FOXO4.
25648147 2015 FOXOs support the metabolic requirements of normal and tumor cells by promoting IDH1 expression.
25609649 2015 Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes.
25416956 2014 A proteome-scale map of the human interactome network.
25053419 2014 GSK3 protein positively regulates type I insulin-like growth factor receptor through forkhead transcription factors FOXO1/3/4.
25007147 2014 A novel CIC-FOXO4 gene fusion in undifferentiated small round cell sarcoma: a genetically distinct variant of Ewing-like sarcoma.
24984152 2014 Cleaved high molecular weight kininogen stimulates JNK/FOXO4/MnSOD pathway for induction of endothelial progenitor cell senescence.
24983969 2014 A genome-wide RNAi screen identifies FOXO4 as a metastasis-suppressor through counteracting PI3K/AKT signal pathway in prostate cancer.
24935588 2014 Low expression of the FoxO4 gene may contribute to the phenomenon of EMT in non-small cell lung cancer.
24886657 2014 The transcription factor FOXO4 is down-regulated and inhibits tumor proliferation and metastasis in gastric cancer.
24663349 2014 FOXO4-knockdown suppresses oxidative stress-induced apoptosis of early pro-angiogenic cells and augments their neovascularization capacities in ischemic limbs.
24353279 2014 FoxO4 interacts with the sterol regulatory factor SREBP2 and the hypoxia inducible factor HIF2? at the CYP51 promoter.
23770673 2013 The small GTPase RALA controls c-Jun N-terminal kinase-mediated FOXO activation by regulation of a JIP1 scaffold complex.
23707940 2013 miR-421 induces cell proliferation and apoptosis resistance in human nasopharyngeal carcinoma via downregulation of FOXO4.
23551888 2013 FOXO4 is necessary for neural differentiation of human embryonic stem cells.
23333309 2013 Redox-dependent control of FOXO/DAF-16 by transportin-1.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
22972301 2012 Increased proteasome activity in human embryonic stem cells is regulated by PSMD11.
22411791 2012 Regulation of neuroblastoma differentiation by forkhead transcription factors FOXO1/3/4 through the receptor tyrosine kinase PDGFRA.
22285440 2012 Screening for mutations of the FOXO4 gene in premature ovarian failure patients.
22125836 2011 [Expression and clinical significance of FOX04 in colorectal cancer].
22112832 2012 Human labour is associated with decreased cytoplasmic FoxO4.
21934092 2011 MicroRNA-499-5p promotes cellular invasion and tumor metastasis in colorectal cancer by targeting FOXO4 and PDCD4.
21708191 2011 FoxO transcription factors; Regulation by AKT and 14-3-3 proteins.
21613825 2011 FoxO family members in cancer.
21567078 2011 Up-regulation of Foxo4 mediated by hepatitis B virus X protein confers resistance to oxidative stress-induced cell death.
21536589 2011 FOXO4-dependent upregulation of superoxide dismutase-2 in response to oxidative stress is impaired in spinocerebellar ataxia type 3.
21525355 2011 The human T-cell leukemia virus type 1 oncoprotein tax controls forkhead box O4 activity through degradation by the proteasome.
21510935 2011 FoxO regulates expression of decidual protein induced by progesterone (DEPP) in human endothelial cells.
21454807 2011 Adiponectin induces vascular smooth muscle cell differentiation via repression of mammalian target of rapamycin complex 1 and FoxO4.
21388494 2011 Candidate gene study of FOXO1, FOXO4, and FOXO6 reveals no association with human longevity in Germans.
21123876 2010 Structure of the human FOXO4-DBD-DNA complex at 1.9?Å resolution reveals new details of FOXO binding to the DNA.
20934750 2010 Expression and localisation of FoxO3 and FoxO4 in human placenta and fetal membranes.
20874444 2011 Oxidative stress-dependent regulation of Forkhead box O4 activity by nemo-like kinase.
20570964 2010 The DNA damage repair protein Ku70 interacts with FOXO4 to coordinate a conserved cellular stress response.
20348951 2010 PKG inhibits TCF signaling in colon cancer cells by blocking beta-catenin expression and activating FOXO4.
20136501 2010 FOXO4 induces human plasminogen activator inhibitor-1 gene expression via an indirect mechanism by modulating HIF-1alpha and CREB levels.
20037138 2010 Effects of FoxO4 overexpression on cholesterol biosynthesis, triacylglycerol accumulation, and glucose uptake.
19932102 2010 O-GlcNAcylation enhances FOXO4 transcriptional regulation in response to stress.
19560465 2009 FoxO4 inhibits NF-kappaB and protects mice against colonic injury and inflammation.
19416966 2009 14-3-3 protein masks the DNA binding interface of forkhead transcription factor FOXO4.
19244250 2009 The transcription of FOXO genes is stimulated by FOXO3 and repressed by growth factors.
18794148 2008 The peptidyl-isomerase Pin1 regulates p27kip1 expression through inhibition of Forkhead box O tumor suppressors.
18692812 2009 Expression of forkhead transcription factors in human granulosa cells.
18665269 2008 Mdm2 induces mono-ubiquitination of FOXO4.
18648506 2008 Splice variants of the forkhead box protein AFX exhibit dominant negative activity and inhibit AFXalpha-mediated tumor cell apoptosis.
17244620 2007 Both the N-terminal loop and wing W2 of the forkhead domain of transcription factor Foxo4 are important for DNA binding.
16964248 2006 FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP.
16571842 2006 Polymorphisms in FOXO gene family and association analysis with BMI.
16272144 2005 Regulation of intracellular localization and transcriptional activity of FOXO4 by protein kinase B through phosphorylation at the motif sites conserved among the FOXO family.
16215946 2005 [Detection of fusion genes resulting from chromosome abnormalities in childhood acute lymphoblastic leukemia].
16114898 2005 14-3-3 Protein interacts with nuclear localization sequence of forkhead transcription factor FoxO4.
16054032 2005 Phenotypic modulation of smooth muscle cells through interaction of Foxo4 and myocardin.
15905404 2005 Functional interaction between beta-catenin and FOXO in oxidative stress signaling.
15824087 2005 FOXO-dependent expression of the proapoptotic protein Bim: pivotal role for apoptosis signaling in endothelial progenitor cells.
15772651 2005 The DNA sequence of the human X chromosome.
15688030 2005 Constitutively active FOXO4 inhibits Akt activity, regulates p27 Kip1 stability, and suppresses HER2-mediated tumorigenicity.
15688004 2005 Activation of FoxO transcription factors contributes to the antiproliferative effect of cAMP.
15538382 2004 FOXO transcription factor activation by oxidative stress mediated by the small GTPase Ral and JNK.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15342556 2004 Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions.
15126506 2004 FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1).
15084259 2004 Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation.
14690436 2003 Two 14-3-3 binding motifs are required for stable association of Forkhead transcription factor FOXO4 with 14-3-3 proteins and inhibition of DNA binding.
12964026 2003 Negative regulation of forkhead transcription factor AFX (Foxo4) by CBP-induced acetylation.
12960271 2003 Neutrophil activation by fMLP regulates FOXO (forkhead) transcription factors by multiple pathways, one of which includes the binding of FOXO to the survival factor Mcl-1.
12761217 2003 The forkhead transcription factor FOXO4 induces the down-regulation of hypoxia-inducible factor 1 alpha by a von Hippel-Lindau protein-independent mechanism.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12192052 2002 MLL-AFX requires the transcriptional effector domains of AFX to transform myeloid progenitors and transdominantly interfere with forkhead protein function.
11884591 2002 Control of cell cycle exit and entry by protein kinase B-regulated forkhead transcription factors.
11779849 2002 An mRNA splice variant of the AFX gene with altered transcriptional activity.
11777915 2002 The forkhead transcription factor AFX activates apoptosis by induction of the BCL-6 transcriptional repressor.
11689711 2001 Regulation of the Forkhead transcription factor AFX by Ral-dependent phosphorylation of threonines 447 and 451.
11435445 2001 Ligand-dependent interaction of estrogen receptor-alpha with members of the forkhead transcription factor family.
11352721 2001 Solution structure of the DNA binding domain of the human forkhead transcription factor AFX (FOXO4).
11313479 2001 Inhibition of nuclear import by protein kinase B (Akt) regulates the subcellular distribution and activity of the forkhead transcription factor AFX.
10973497 2000 DAF-16 recruits the CREB-binding protein coactivator complex to the insulin-like growth factor binding protein 1 promoter in HepG2 cells.
10921784 2000 1H, 13C and 15N resonance assignments of the DNA binding domain of the human forkhead transcription factor AFX.
10880363 2000 Identification of the differential distribution patterns of mRNAs and consensus binding sequences for mouse DAF-16 homologues.
10783894 2000 AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1.
10518537 1999 Regulation of nuclear translocation of forkhead transcription factor AFX by protein kinase B.
10217147 1999 Direct control of the Forkhead transcription factor AFX by protein kinase B.
9341872 1997 AFX1 and p54nrb: fine mapping, genomic structure, and exclusion as candidate genes of X-linked dystonia parkinsonism.
9010221 1997 Cloning and characterization of AFX, the gene that fuses to MLL in acute leukemias with a t(X;11)(q13;q23).
7529552 1994 Cloning and characterization of the t(X;11) breakpoint from a leukemic cell line identify a new member of the forkhead gene family.