FKHR

Summary

Gene Symbol: FKHR
Description: forkhead box O1
Alias: FKH1, FKHR, FOXO1A, forkhead box protein O1, forkhead box protein O1A, forkhead, Drosophila, homolog of, in rhabdomyosarcoma
Species: human
Products:     FKHR

Top Publications

  1. Matsuzaki H, Daitoku H, Hatta M, Tanaka K, Fukamizu A. Insulin-induced phosphorylation of FKHR (Foxo1) targets to proteasomal degradation. Proc Natl Acad Sci U S A. 2003;100:11285-90 pubmed
    Forkhead transcription factor FKHR (Foxo1) is a key regulator of glucose homeostasis, cell-cycle progression, and apoptosis...
  2. Zeng Z, Lin H, Zhao X, Liu G, Wang X, Xu R, et al. Overexpression of GOLPH3 promotes proliferation and tumorigenicity in breast cancer via suppression of the FOXO1 transcription factor. Clin Cancer Res. 2012;18:4059-69 pubmed publisher
    ..Our results suggest that high GOLPH3 expression is associated with poor overall survival in patients with breast cancer and that GOLPH3 overexpression increases the proliferation and tumorigenicity of human breast cancer cells. ..
  3. Li Y, Wang W, Cao H, Lu J, Wu C, Hu F, et al. Genetic association of FOXO1A and FOXO3A with longevity trait in Han Chinese populations. Hum Mol Genet. 2009;18:4897-904 pubmed publisher
    b>FOXO1A and FOXO3A are two members of the FoxO family. FOXO3A has recently been linked to human longevity in Japanese, German and Italian populations...
  4. Kloet D, Burgering B. The PKB/FOXO switch in aging and cancer. Biochim Biophys Acta. 2011;1813:1926-37 pubmed publisher
    ..This article is part of a Special Issue entitled: P13K-AKT-FoxO axis in cancer and aging. ..
  5. Rena G, Guo S, Cichy S, Unterman T, Cohen P. Phosphorylation of the transcription factor forkhead family member FKHR by protein kinase B. J Biol Chem. 1999;274:17179-83 pubmed
    ..Here we show that FKHR, a human homologue of the DAF16 transcription factor in Caenorhabditis elegans, is rapidly phosphorylated by human ..
  6. Christian M, Zhang X, Schneider Merck T, Unterman T, Gellersen B, White J, et al. Cyclic AMP-induced forkhead transcription factor, FKHR, cooperates with CCAAT/enhancer-binding protein beta in differentiating human endometrial stromal cells. J Biol Chem. 2002;277:20825-32 pubmed
    ..We now report on the role of forkhead homologue in rhabdomyosarcoma (FKHR), a recently described member of the forkhead/winged-helix transcription factor family, as a mediator of ..
  7. Anderson M, Viars C, Czekay S, Cavenee W, Arden K. Cloning and characterization of three human forkhead genes that comprise an FKHR-like gene subfamily. Genomics. 1998;47:187-99 pubmed
    ..and t(1;13), which arise from fusion of the genes for the paired box proteins PAX3 and PAX7, respectively, to the FKHR (forkhead in rhabdomyosarcoma) gene on chromosome 13q14...
  8. Sumegi J, Streblow R, Frayer R, Dal Cin P, Rosenberg A, Meloni Ehrig A, et al. Recurrent t(2;2) and t(2;8) translocations in rhabdomyosarcoma without the canonical PAX-FOXO1 fuse PAX3 to members of the nuclear receptor transcriptional coactivator family. Genes Chromosomes Cancer. 2010;49:224-36 pubmed publisher
    ..The latter could potentially be used as aids in diagnostically challenging cases...
  9. Matsuzaki H, Daitoku H, Hatta M, Aoyama H, Yoshimochi K, Fukamizu A. Acetylation of Foxo1 alters its DNA-binding ability and sensitivity to phosphorylation. Proc Natl Acad Sci U S A. 2005;102:11278-83 pubmed
    ..These results suggest that acetylation regulates the function of Foxo1 through altering the affinity with the target DNA and the sensitivity for phosphorylation. ..

More Information

Publications99

  1. Fredericks W, Galili N, Mukhopadhyay S, Rovera G, Bennicelli J, Barr F, et al. The PAX3-FKHR fusion protein created by the t(2;13) translocation in alveolar rhabdomyosarcomas is a more potent transcriptional activator than PAX3. Mol Cell Biol. 1995;15:1522-35 pubmed
    ..chromosome involved in this translocation have been identified as the transcription factor-encoding genes PAX3 and FKHR. The NH2-terminal paired box and homeodomain DNA-binding domains of PAX3 are fused in frame to COOH-terminal ..
  2. Ward E, Hoekstra A, Blok L, Hanifi Moghaddam P, Lurain J, Singh D, et al. The regulation and function of the forkhead transcription factor, Forkhead box O1, is dependent on the progesterone receptor in endometrial carcinoma. Endocrinology. 2008;149:1942-50 pubmed
    ..Taken together, these data provide insight into the phosphoinositide-3-kinase/Akt/FOXO pathway for the determination of progestin responsiveness and the development of alternate therapies for endometrial cancer. ..
  3. Yang Y, Zhao Y, Liao W, Yang J, Wu L, Zheng Z, et al. Acetylation of FoxO1 activates Bim expression to induce apoptosis in response to histone deacetylase inhibitor depsipeptide treatment. Neoplasia. 2009;11:313-24 pubmed
    ..These data show for the first time that an HDAC inhibitor induces apoptosis through the FoxO1 acetylation-Bim pathway. ..
  4. Guttilla I, White B. Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells. J Biol Chem. 2009;284:23204-16 pubmed publisher
    ..We have identified a novel mechanism of FOXO1 regulation, and targeting of FOXO1 by microRNAs may contribute to transformation or maintenance of an oncogenic state in breast cancer cells. ..
  5. Huang H, Muddiman D, Tindall D. Androgens negatively regulate forkhead transcription factor FKHR (FOXO1) through a proteolytic mechanism in prostate cancer cells. J Biol Chem. 2004;279:13866-77 pubmed
    ..However, the underlying mechanisms are understood poorly. Here we demonstrated that forkhead transcription factor FKHR (FOXO1)-induced death of LNCaP cells was blocked by a synthetic androgen R1881...
  6. Xie L, Ushmorov A, Leithäuser F, Guan H, Steidl C, Färbinger J, et al. FOXO1 is a tumor suppressor in classical Hodgkin lymphoma. Blood. 2012;119:3503-11 pubmed publisher
    ..These results suggest that FOXO1 repression contributes to cHL lymphomagenesis. ..
  7. Müssig K, Staiger H, Machicao F, Stancakova A, Kuusisto J, Laakso M, et al. Association of common genetic variation in the FOXO1 gene with beta-cell dysfunction, impaired glucose tolerance, and type 2 diabetes. J Clin Endocrinol Metab. 2009;94:1353-60 pubmed publisher
    ..The objective of the study was to investigate whether common genetic variation within the FOXO1 gene encoding FOXO1A contributes to prediabetic phenotypes, such as insulin resistance or beta-cell dysfunction, and to risk of type 2 ..
  8. Tzivion G, Dobson M, Ramakrishnan G. FoxO transcription factors; Regulation by AKT and 14-3-3 proteins. Biochim Biophys Acta. 2011;1813:1938-45 pubmed publisher
    ..This article is part of a Special Issue entitled: PI3K-AKT-FoxO axis in cancer and aging. ..
  9. Marshall A, Picchione F, Geltink R, Grosveld G. PAX3-FOXO1 induces up-regulation of Noxa sensitizing alveolar rhabdomyosarcoma cells to apoptosis. Neoplasia. 2013;15:738-48 pubmed
    ..Most ARMS tumors characteristically possess a specific genomic translocation between the genes of PAX3/7 and FOXO1 (FKHR), which forms fusion proteins possessing the DNA binding domains of PAX3/7 and the more transcriptionally potent ..
  10. Fan W, Yanase T, Morinaga H, Okabe T, Nomura M, Daitoku H, et al. Insulin-like growth factor 1/insulin signaling activates androgen signaling through direct interactions of Foxo1 with androgen receptor. J Biol Chem. 2007;282:7329-38 pubmed
  11. Alikhani M, Alikhani Z, Graves D. FOXO1 functions as a master switch that regulates gene expression necessary for tumor necrosis factor-induced fibroblast apoptosis. J Biol Chem. 2005;280:12096-102 pubmed
    ..siRNA silencing also blocked down-regulation of anti-apoptotic genes. These results indicate that TNF induces activation of the FOXO1 transcription factor, which acts as a master switch to control apoptosis. ..
  12. Cheong J, Eom J, Maeng H, Lee S, Hahn J, Ko Y, et al. Constitutive phosphorylation of FKHR transcription factor as a prognostic variable in acute myeloid leukemia. Leuk Res. 2003;27:1159-62 pubmed
    The transcription factor FKHR, which is controlled by Akt-PKB signaling, is involved in regulating cell cycle progression and cell death. In this study, the phosphorylation of FKHR was observed in 45 (73...
  13. Fabre S, Carrette F, Chen J, Lang V, Semichon M, Denoyelle C, et al. FOXO1 regulates L-Selectin and a network of human T cell homing molecules downstream of phosphatidylinositol 3-kinase. J Immunol. 2008;181:2980-9 pubmed
    ..Together, these results reveal a new function of FOXO1 in the immune system and suggest that PI3K controls a coordinated network of transcription factors regulating both cell quiescence and homing of human T lymphocytes. ..
  14. Kawamori D, Kaneto H, Nakatani Y, Matsuoka T, Matsuhisa M, Hori M, et al. The forkhead transcription factor Foxo1 bridges the JNK pathway and the transcription factor PDX-1 through its intracellular translocation. J Biol Chem. 2006;281:1091-8 pubmed
    ..In this study, we have shown that the forkhead transcription factor Foxo1/FKHR plays a role as a mediator between the JNK pathway and PDX-1...
  15. Zhang Y, Gan B, Liu D, Paik J. FoxO family members in cancer. Cancer Biol Ther. 2011;12:253-9 pubmed
  16. Du S, Lawrence E, Strzelecki D, Rajput P, Xia S, Gottesman D, et al. Co-expression of alternatively spliced forms of PAX3, PAX7, PAX3-FKHR and PAX7-FKHR with distinct DNA binding and transactivation properties in rhabdomyosarcoma. Int J Cancer. 2005;115:85-92 pubmed
    ..pathogenesis of rhabdomyosarcoma (RMS), including alveolar RMS in which chromosomal translocations generate PAX3-FKHR and PAX7-FKHR fusions...
  17. Zhang Y, Wang C. Nephroblastoma overexpressed (NOV/CCN3) gene: a paired-domain-specific PAX3-FKHR transcription target that promotes survival and motility in alveolar rhabdomyosarcoma cells. Oncogene. 2011;30:3549-62 pubmed publisher
    ..Over 80% of aRMSs are characterized by a chromosomal translocation-derived fusion transcription factor PAX3-FKHR. In this study, we linked elevated CCN3 levels in aRMS cells to PAX3-FKHR expression...
  18. Kleindorp R, Flachsbart F, Puca A, Malovini A, Schreiber S, Nebel A. Candidate gene study of FOXO1, FOXO4, and FOXO6 reveals no association with human longevity in Germans. Aging Cell. 2011;10:622-8 pubmed publisher
    ..The discrepant association findings in Europeans and Chinese may be explained by their different FOXO1 linkage disequilibrium structures and could indicate a Chinese- or Asian-specific effect. ..
  19. Scheidler S, Fredericks W, Rauscher F, Barr F, Vogt P. The hybrid PAX3-FKHR fusion protein of alveolar rhabdomyosarcoma transforms fibroblasts in culture. Proc Natl Acad Sci U S A. 1996;93:9805-9 pubmed
    Pediatric alveolar rhabdomyosarcoma is characterized by a chromosomal translocation that fuses parts of the PAX3 and FKHR genes...
  20. Scuoppo C, Riess I, Schmitt Ney M, Allegra P, Forni P, Bersani F, et al. The oncogenic transcription factor PAX3-FKHR can convert fibroblasts into contractile myotubes. Exp Cell Res. 2007;313:2308-17 pubmed
    PAX3-FKHR, the product of a rearrangement of PAX3 with FKHR is the pathogenetic marker for alveolar rhabdomyosarcoma, an aggressive form of childhood cancer...
  21. Wu L, Li H, Jia C, Cheng W, Yu M, Peng M, et al. MicroRNA-223 regulates FOXO1 expression and cell proliferation. FEBS Lett. 2012;586:1038-43 pubmed publisher
    ..Proliferation of the cells was also greatly inhibited when miR-223 was over-expressed. Therein, our data suggest that miR-223 regulates FOXO1 expression and cell proliferation. ..
  22. Huang H, Regan K, Lou Z, Chen J, Tindall D. CDK2-dependent phosphorylation of FOXO1 as an apoptotic response to DNA damage. Science. 2006;314:294-7 pubmed
    ..Functional interaction between CDK2 and FOXO1 provides a mechanism that regulates apoptotic cell death after DNA strand breakage. ..
  23. Dong X, Chen C, Sun X, Guo P, Vessella R, Wang R, et al. FOXO1A is a candidate for the 13q14 tumor suppressor gene inhibiting androgen receptor signaling in prostate cancer. Cancer Res. 2006;66:6998-7006 pubmed
    ..lines/xenografts of prostate cancer mapped the deletion locus to 919 kb, which harbors only one known gene, the FOXO1A transcription factor...
  24. Li R, Erdamar S, Dai H, Wheeler T, Frolov A, Scardino P, et al. Forkhead protein FKHR and its phosphorylated form p-FKHR in human prostate cancer. Hum Pathol. 2007;38:1501-7 pubmed
    In vitro studies suggest that the proapoptotic function of forkhead protein FKHR is probably inactivated by means of phosphorylation through the protein kinase B pathway...
  25. Fu W, Ma Q, Chen L, Li P, Zhang M, Ramamoorthy S, et al. MDM2 acts downstream of p53 as an E3 ligase to promote FOXO ubiquitination and degradation. J Biol Chem. 2009;284:13987-4000 pubmed publisher
    ..These data suggest that MDM2 acts as an ubiquitin E3 ligase, downstream of p53, to regulate the degradation of mammalian FOXO factors. ..
  26. Yang Y, Hou H, Haller E, Nicosia S, Bai W. Suppression of FOXO1 activity by FHL2 through SIRT1-mediated deacetylation. EMBO J. 2005;24:1021-32 pubmed
    ..FHL2 enhanced the interaction of FOXO1 and SIRT1 and the deacetylation of FOXO1 by Sirtuin-1 (SIRT1). Overall, our data show that FHL2 inhibits FOXO1 activity in prostate cancer cells by promoting the deacetylation of FOXO1 by SIRT1. ..
  27. Cao Y, Kamioka Y, Yokoi N, Kobayashi T, Hino O, Onodera M, et al. Interaction of FoxO1 and TSC2 induces insulin resistance through activation of the mammalian target of rapamycin/p70 S6K pathway. J Biol Chem. 2006;281:40242-51 pubmed
    ..These data suggest a novel mechanism by which FoxO1 regulates the insulin signaling pathway through negative regulation of TSC2 function. ..
  28. Xia S, Holder D, Pawel B, Zhang C, Barr F. High expression of the PAX3-FKHR oncoprotein is required to promote tumorigenesis of human myoblasts. Am J Pathol. 2009;175:2600-8 pubmed publisher
    PAX3-FKHR is a fusion oncoprotein generated by the 2;13 chromosomal translocation in alveolar rhabdomyosarcoma (ARMS), a cancer associated with the skeletal muscle lineage...
  29. Ramaswamy S, Nakamura N, Sansal I, Bergeron L, Sellers W. A novel mechanism of gene regulation and tumor suppression by the transcription factor FKHR. Cancer Cell. 2002;2:81-91 pubmed
    The mammalian DAF-16-like transcription factors, FKHR, FKHRL1, and AFX, function as key regulators of insulin signaling, cell cycle progression, and apoptosis downstream of phosphoinositide 3-kinase...
  30. Zhang X, Tang N, Hadden T, Rishi A. Akt, FoxO and regulation of apoptosis. Biochim Biophys Acta. 2011;1813:1978-86 pubmed publisher
    ..This article is part of a Special Issue entitled: P13K-AKT-FOxO axis in cancer and aging. ..
  31. Ebauer M, Wachtel M, Niggli F, Schafer B. Comparative expression profiling identifies an in vivo target gene signature with TFAP2B as a mediator of the survival function of PAX3/FKHR. Oncogene. 2007;26:7267-81 pubmed
    ..the aggressive childhood cancer alveolar rhabdomyosarcoma (aRMS), generates the chimeric transcription factor PAX3/FKHR with a well known oncogenic role...
  32. Kwon H, Huang B, Unterman T, Harris R. Protein kinase B-alpha inhibits human pyruvate dehydrogenase kinase-4 gene induction by dexamethasone through inactivation of FOXO transcription factors. Diabetes. 2004;53:899-910 pubmed
    ..alpha abrogates dexamethasone stimulation of hPDK4 promoter activity, while coexpression of constitutively active FOXO1a or FOXO3a, which are mutated to alanine at the three phosphorylation sites for protein kinase B (PKB), disrupts ..
  33. Labied S, Kajihara T, Madureira P, Fusi L, Jones M, Higham J, et al. Progestins regulate the expression and activity of the forkhead transcription factor FOXO1 in differentiating human endometrium. Mol Endocrinol. 2006;20:35-44 pubmed
  34. Daitoku H, Yamagata K, Matsuzaki H, Hatta M, Fukamizu A. Regulation of PGC-1 promoter activity by protein kinase B and the forkhead transcription factor FKHR. Diabetes. 2003;52:642-9 pubmed
    ..Here, we show that forkhead transcription factor FKHR contributes to mediating the effects of insulin on PGC-1 promoter activity...
  35. Shore A, White P, Hui R, Essafi A, Lam E, Rowe M, et al. Epstein-Barr virus represses the FoxO1 transcription factor through latent membrane protein 1 and latent membrane protein 2A. J Virol. 2006;80:11191-9 pubmed publisher
    ..Expression of the EBV genes for latent membrane protein 1 and latent membrane protein 2A decreases FoxO1 expression. Thus, our data elucidate distinct mechanisms for the regulation of the proapoptotic transcription factor FoxO1 by EBV...
  36. Qiang L, Tsuchiya K, Kim Muller J, Lin H, Welch C, Accili D. Increased atherosclerosis and endothelial dysfunction in mice bearing constitutively deacetylated alleles of Foxo1 gene. J Biol Chem. 2012;287:13944-51 pubmed publisher
    ..The data indicate that FoxO1 deacetylation can promote vascular endothelial changes conducive to atherosclerotic plaque formation. ..
  37. Tejera M, Kim E, Sullivan J, Plisch E, Suresh M. FoxO1 controls effector-to-memory transition and maintenance of functional CD8 T cell memory. J Immunol. 2013;191:187-99 pubmed publisher
    ..These findings have provided fundamental insights into the mechanisms that regulate the quality of CD8 T cell memory to intracellular pathogens. ..
  38. Kato S, Ding J, Pisck E, Jhala U, Du K. COP1 functions as a FoxO1 ubiquitin E3 ligase to regulate FoxO1-mediated gene expression. J Biol Chem. 2008;283:35464-73 pubmed publisher
    ..We suggest that by functioning as a FoxO1 E3 ligase, COP1 may play a role in the regulation of hepatic glucose metabolism. ..
  39. Kim J, Taylor H, Akbas G, Foucher I, Trembleau A, Jaffe R, et al. Regulation of insulin-like growth factor binding protein-1 promoter activity by FKHR and HOXA10 in primate endometrial cells. Biol Reprod. 2003;68:24-30 pubmed
    ..b>FKHR, a FOXO forkhead transcription factor, stimulates IGFBP-1 promoter activity in liver cells through the insulin ..
  40. Jung Y, Lee K, Kim M, Jung G, Seo Y, Kim H, et al. Forkhead transcription factor FoxO1 inhibits insulin- and transforming growth factor-beta-stimulated plasminogen activator inhibitor-1 expression. Biochem Biophys Res Commun. 2009;386:757-61 pubmed publisher
    ..Our data also suggest that in the hyperinsulinemic state, FoxO1 is inactivated by increased levels of insulin, and does not function as an inhibitor of TGF-beta-induced PAI-1 expression. ..
  41. Amstutz R, Wachtel M, Troxler H, Kleinert P, Ebauer M, Haneke T, et al. Phosphorylation regulates transcriptional activity of PAX3/FKHR and reveals novel therapeutic possibilities. Cancer Res. 2008;68:3767-76 pubmed publisher
    ..aRMS), in which specific translocations lead to the formation of the chimeric transcription factor PAX3/FKHR. Here, we found unexpectedly that the transcriptional activity of PAX3/FKHR can be inhibited by the kinase ..
  42. Zhao X, Gan L, Pan H, Kan D, Majeski M, Adam S, et al. Multiple elements regulate nuclear/cytoplasmic shuttling of FOXO1: characterization of phosphorylation- and 14-3-3-dependent and -independent mechanisms. Biochem J. 2004;378:839-49 pubmed
    ..The presence of these redundant mechanisms supports the concept that the regulation of FOXO1 function plays a critical role in insulin and growth factor action. ..
  43. Buzzio O, Lu Z, Miller C, Unterman T, Kim J. FOXO1A differentially regulates genes of decidualization. Endocrinology. 2006;147:3870-6 pubmed
    The forkhead box O1A (FOXO1A) has been identified as one gene that is up-regulated early in the decidualization process...
  44. Huang H, Tindall D. Regulation of FOXO protein stability via ubiquitination and proteasome degradation. Biochim Biophys Acta. 2011;1813:1961-4 pubmed publisher
    ..This article is part of a Special Issue entitled: PI3K-AKT-FoxO axis in cancer and aging. ..
  45. Melnik B. FoxO1 - the key for the pathogenesis and therapy of acne?. J Dtsch Dermatol Ges. 2010;8:105-14 pubmed publisher
    ..Various receptor-mediated growth factor signals are integrated at the level of PI3K/Akt activation which finally results in nuclear FoxO1 deficiency. ..
  46. Hay N. Interplay between FOXO, TOR, and Akt. Biochim Biophys Acta. 2011;1813:1965-70 pubmed publisher
    ..The biological significance of these regulatory circuits is discussed in this article. This article is part of a Special Issue entitled: P13K-AKT-FoxO axis in cancer and aging. ..
  47. Lagutina I, Conway S, Sublett J, Grosveld G. Pax3-FKHR knock-in mice show developmental aberrations but do not develop tumors. Mol Cell Biol. 2002;22:7204-16 pubmed
    ..These translocations result in the formation of the PAX3-FKHR and PAX7-FKHR fusion genes, which are thought to play a causal role in the genesis of this disease...
  48. Yang L, Hu H, Zielinska Kwiatkowska A, Chansky H. FOXO1 is a direct target of EWS-Fli1 oncogenic fusion protein in Ewing's sarcoma cells. Biochem Biophys Res Commun. 2010;402:129-34 pubmed publisher
    ..Together, these results suggest that suppression of FOXO1 function by EWS-Fli1 fusion protein may contribute to cellular transformation in Ewing's family tumors. ..
  49. Kikuchi K, Tsuchiya K, Otabe O, Gotoh T, Tamura S, Katsumi Y, et al. Effects of PAX3-FKHR on malignant phenotypes in alveolar rhabdomyosarcoma. Biochem Biophys Res Commun. 2008;365:568-74 pubmed
    The malignancy of alveolar rhabdomyosarcoma (ARMS) has been linked to expression of the PAX3-FKHR chimeric gene...
  50. Aoki M, Jiang H, Vogt P. Proteasomal degradation of the FoxO1 transcriptional regulator in cells transformed by the P3k and Akt oncoproteins. Proc Natl Acad Sci U S A. 2004;101:13613-7 pubmed
    ..The FoxG1 oncoprotein also inhibits transcriptional activation by FoxO1. Inhibition of FoxO1, albeit by different mechanisms, appears to be a common denominator of the PI3K and FoxG1 oncogenic pathways. ..
  51. Begum S, Emami N, Emani N, Cheung A, Wilkins O, Der S, et al. Cell-type-specific regulation of distinct sets of gene targets by Pax3 and Pax3/FKHR. Oncogene. 2005;24:1860-72 pubmed
    The oncogenic fusion protein, Pax3/FKHR, is a more potent transcription factor relative to its normal counterpart, Pax3...
  52. Wu Z, Sun H, Zeng W, He J, Mao X. Upregulation of MircoRNA-370 induces proliferation in human prostate cancer cells by downregulating the transcription factor FOXO1. PLoS ONE. 2012;7:e45825 pubmed publisher
    b>Forkhead box protein O1 (FOXO1), a key member of the FOXO family of transcription factors, acts as a tumor suppressor and has been associated with various key cellular functions, including cell growth, differentiation, apoptosis and ..
  53. Zhang L, Wang C. Identification of a new class of PAX3-FKHR target promoters: a role of the Pax3 paired box DNA binding domain. Oncogene. 2007;26:1595-605 pubmed
    ..a unique t(2;13) chromosomal translocation resulting in the formation of a chimeric transcription factor PAX3-FKHR. This fusion protein contains the intact DNA-binding domains (PD: paired box binding domain; HD: paired-type ..
  54. Zhao Y, Yang J, Liao W, Liu X, Zhang H, Wang S, et al. Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity. Nat Cell Biol. 2010;12:665-75 pubmed publisher
    ..This FoxO1-modulated cell death is associated with tumour suppressor activity in human colon tumours and a xenograft mouse model. Our finding links the anti-neoplastic activity of FoxO1 and the process of autophagy. ..
  55. Roeb W, Boyer A, Cavenee W, Arden K. PAX3-FOXO1 controls expression of the p57Kip2 cell-cycle regulator through degradation of EGR1. Proc Natl Acad Sci U S A. 2007;104:18085-90 pubmed
    ..Thus, the breakage and fusion of the genes encoding these transcription factors creates a unique chimeric protein that controls a key cell-cycle and -differentiation regulator. ..
  56. Williamson D, Missiaglia E, de Reynies A, Pierron G, Thuille B, Palenzuela G, et al. Fusion gene-negative alveolar rhabdomyosarcoma is clinically and molecularly indistinguishable from embryonal rhabdomyosarcoma. J Clin Oncol. 2010;28:2151-8 pubmed publisher
  57. Zhang H, Pan Y, Zheng L, Choe C, Lindgren B, Jensen E, et al. FOXO1 inhibits Runx2 transcriptional activity and prostate cancer cell migration and invasion. Cancer Res. 2011;71:3257-67 pubmed publisher
  58. Lau C, Koty Z, Nalbantoglu J. Differential response of glioma cells to FOXO1-directed therapy. Cancer Res. 2009;69:5433-40 pubmed publisher
    ..They also highlight the importance of Akt-independent phosphorylation events in the nuclear export of FOXO1. ..
  59. Li P, Lee H, Guo S, Unterman T, Jenster G, Bai W. AKT-independent protection of prostate cancer cells from apoptosis mediated through complex formation between the androgen receptor and FKHR. Mol Cell Biol. 2003;23:104-18 pubmed
    Recent studies suggested that the protection of cell apoptosis by AKT involves phosphorylation and inhibition of FKHR and related FOXO forkhead transcription factors and that androgens provide an AKT-independent cell survival signal in ..
  60. Trinh D, Scott D, Morin R, Mendez Lago M, An J, Jones S, et al. Analysis of FOXO1 mutations in diffuse large B-cell lymphoma. Blood. 2013;121:3666-74 pubmed publisher
    ..The independent relationship of mutations in FOXO1 to survival, transcending the prognostic influence of the R-IPI and COO, indicates that FOXO1 mutation is a novel prognostic factor that plays an important role in DLBCL pathogenesis. ..
  61. Davis R, Bennicelli J, Macina R, Nycum L, Biegel J, Barr F. Structural characterization of the FKHR gene and its rearrangement in alveolar rhabdomyosarcoma. Hum Mol Genet. 1995;4:2355-62 pubmed
    The FKHR gene, which contains a forkhead DNA-binding motif, is fused to either PAX3 or PAX7 by the t(2;13) or t(1;13) translocation in alveolar rhabdomyosarcoma,respectively...
  62. Kim J, Kim M, Lee H, Cho S, Cho Y, Lee B, et al. Constitutive phosphorylation of the FOXO1A transcription factor as a prognostic variable in gastric cancer. Mod Pathol. 2007;20:835-42 pubmed
    Increased phosphorylation of FOXO1A, a FOXO transcription factor, has been implicated in several human cancers; however, it has not been studied in the gastric cancer to date...
  63. Kuo C, Lin S. Altered FOXO1 transcript levels in peripheral blood mononuclear cells of systemic lupus erythematosus and rheumatoid arthritis patients. Mol Med. 2007;13:561-6 pubmed
    ..These data suggest that the transcriptional dysregulation in FOXO1 is possibly linked to the pathogenesis of SLE and RA. ..
  64. Rena G, Prescott A, Guo S, Cohen P, Unterman T. Roles of the forkhead in rhabdomyosarcoma (FKHR) phosphorylation sites in regulating 14-3-3 binding, transactivation and nuclear targetting. Biochem J. 2001;354:605-12 pubmed
    The transcription factor, forkhead in rhabdomyosarcoma (FKHR), is phosphorylated at three amino acid residues (Thr-24, Ser-256 and Ser-319) by protein kinase B (PKB)alpha...
  65. Sorensen P, Lynch J, Qualman S, Tirabosco R, Lim J, Maurer H, et al. PAX3-FKHR and PAX7-FKHR gene fusions are prognostic indicators in alveolar rhabdomyosarcoma: a report from the children's oncology group. J Clin Oncol. 2002;20:2672-9 pubmed
    ..Most ARMS patients express PAX3-FKHR or PAX7-FKHR gene fusions resulting from t(2;13) or t(1;13) translocations, respectively...
  66. Kousteni S. FoxO1: a molecule for all seasons. J Bone Miner Res. 2011;26:912-7 pubmed publisher
  67. Zhang X, Gan L, Pan H, Guo S, He X, Olson S, et al. Phosphorylation of serine 256 suppresses transactivation by FKHR (FOXO1) by multiple mechanisms. Direct and indirect effects on nuclear/cytoplasmic shuttling and DNA binding. J Biol Chem. 2002;277:45276-84 pubmed
    b>FKHR is a member of the FOXO subfamily of Forkhead transcription factors, which are important targets for insulin and growth factor signaling...
  68. Huang H, Regan K, Wang F, Wang D, Smith D, van Deursen J, et al. Skp2 inhibits FOXO1 in tumor suppression through ubiquitin-mediated degradation. Proc Natl Acad Sci U S A. 2005;102:1649-54 pubmed
    Forkhead transcription factors FOXO1 (FKHR), FOXO3a (FKHRL1), and FOXO4 (AFX) play a pivotal role in tumor suppression by inducing growth arrest and apoptosis...
  69. Goto T, Takano M, Albergaria A, Briese J, Pomeranz K, Cloke B, et al. Mechanism and functional consequences of loss of FOXO1 expression in endometrioid endometrial cancer cells. Oncogene. 2008;27:9-19 pubmed
    ..Together, these observations suggest that loss of FOXO1 perturbs endometrial homeostasis, promotes uncontrolled cell proliferation and increases susceptibility to genotoxic insults. ..
  70. Seoane J, Le H, Shen L, Anderson S, Massague J. Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation. Cell. 2004;117:211-23 pubmed
    ..We suggest that the activity of this network confers resistance to TGF-beta-mediated cytostasis during the development of the telencephalic neuroepithelium and in glioblastoma brain tumor cells. ..
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    ..ARMS is characterized by a chromosomal translocation generating the PAX3-FKHR fusion gene...
  73. Picchione F, Pritchard C, Lagutina I, Janke L, Grosveld G. IRIZIO: a novel gene cooperating with PAX3-FOXO1 in alveolar rhabdomyosarcoma (ARMS). Carcinogenesis. 2011;32:452-61 pubmed publisher
    ..Expression of full length IRIZIO cDNA also cooperated with PAX3-FOXO1 in the transformation of Arf-/- myoblasts. Given that IRIZIO is expressed at increased levels in RMS, it might contribute to rhabdomyosarcomagenesis in humans. ..
  74. Galili N, Davis R, Fredericks W, Mukhopadhyay S, Rauscher F, Emanuel B, et al. Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma. Nat Genet. 1993;5:230-5 pubmed
    ..The chromosome 13 gene (FKHR) is identified as a member of the fork head domain family of transcription factors characterized by a conserved DNA ..
  75. Tang E, Nunez G, Barr F, Guan K. Negative regulation of the forkhead transcription factor FKHR by Akt. J Biol Chem. 1999;274:16741-6 pubmed
    The FKHR gene was first identified from its disruption by the t(2;13) chromosomal translocation seen in the pediatric tumor alveolar rhabdomyosarcoma. It encodes for a member of the forkhead family of transcription factors...
  76. Medema R, Kops G, Bos J, Burgering B. AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1. Nature. 2000;404:782-7 pubmed
    The Forkhead transcription factors AFX, FKHR and FKHR-L1 are orthologues of DAF-16, a Forkhead factor that regulates longevity in Caenorhabditis elegans...
  77. Yuan Z, Lehtinen M, Merlo P, Villen J, Gygi S, Bonni A. Regulation of neuronal cell death by MST1-FOXO1 signaling. J Biol Chem. 2009;284:11285-92 pubmed publisher
    ..Collectively, these findings define MST1-FOXO1 signaling as an important link survival factor deprivation-induced neuronal cell death with implications for our understanding of brain development and neurological diseases. ..
  78. Essaghir A, Dif N, Marbehant C, Coffer P, Demoulin J. The transcription of FOXO genes is stimulated by FOXO3 and repressed by growth factors. J Biol Chem. 2009;284:10334-42 pubmed publisher
    ..Altogether, our 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. ..
  79. Zeng F, Cui J, Liu L, Chen T. PAX3-FKHR sensitizes human alveolar rhabdomyosarcoma cells to camptothecin-mediated growth inhibition and apoptosis. Cancer Lett. 2009;284:157-64 pubmed publisher
    ..Ectopic expression of the PAX3-FKHR (PF) fusion protein in RD cells significantly increased sensitivity, whereas siRNA knockdown of PF decreased ..
  80. Chen C, Jeon S, Bhaskar P, Nogueira V, Sundararajan D, Tonic I, et al. FoxOs inhibit mTORC1 and activate Akt by inducing the expression of Sestrin3 and Rictor. Dev Cell. 2010;18:592-604 pubmed publisher
    ..Thus, under stress conditions, FoxO inhibits the anabolic activity of mTORC1, a major consumer of cellular energy, while activating Akt, which increases cellular energy metabolism, thereby maintaining cellular energy homeostasis. ..
  81. Yamagata K, Daitoku H, Takahashi Y, Namiki K, Hisatake K, Kako K, et al. Arginine methylation of FOXO transcription factors inhibits their phosphorylation by Akt. Mol Cell. 2008;32:221-31 pubmed publisher
    ..Our findings predict a role for arginine methylation as an inhibitory modification against Akt-mediated phosphorylation. ..
  82. Liu P, Kao T, Huang H. CDK1 promotes cell proliferation and survival via phosphorylation and inhibition of FOXO1 transcription factor. Oncogene. 2008;27:4733-44 pubmed publisher
  83. Berry F, Skarie J, Mirzayans F, Fortin Y, Hudson T, Raymond V, et al. FOXC1 is required for cell viability and resistance to oxidative stress in the eye through the transcriptional regulation of FOXO1A. Hum Mol Genet. 2008;17:490-505 pubmed
    ..FOXC1 regulates the expression of FOXO1A and binds to a conserved element in the FOXO1A promoter in vivo...
  84. Kitamura Y, Kitamura T, Kruse J, Raum J, Stein R, Gu W, et al. FoxO1 protects against pancreatic beta cell failure through NeuroD and MafA induction. Cell Metab. 2005;2:153-63 pubmed
    ..The findings provide a mechanism linking glucose- and growth factor receptor-activated pathways to protect beta cells against oxidative damage via FoxO proteins. ..
  85. Potente M, Urbich C, Sasaki K, Hofmann W, Heeschen C, Aicher A, et al. Involvement of Foxo transcription factors in angiogenesis and postnatal neovascularization. J Clin Invest. 2005;115:2382-92 pubmed
    ..In vivo, Foxo3a deficiency increased eNOS expression and enhanced postnatal vessel formation and maturation. Thus, our data suggest an important role for Foxo transcription factors in the regulation of vessel formation in the adult. ..
  86. Daitoku H, Hatta M, Matsuzaki H, Aratani S, Ohshima T, Miyagishi M, et al. Silent information regulator 2 potentiates Foxo1-mediated transcription through its deacetylase activity. Proc Natl Acad Sci U S A. 2004;101:10042-7 pubmed
    ..Here we show that reversible acetylation of Foxo1 (also known as FKHR), the mouse DAF-16 ortholog, modulates its transactivation function...
  87. Zhou J, Liao W, Yang J, Ma K, Li X, Wang Y, et al. FOXO3 induces FOXO1-dependent autophagy by activating the AKT1 signaling pathway. Autophagy. 2012;8:1712-23 pubmed publisher
    ..To the best of our knowledge, our data are the first to suggest that FOXO1 plays a central role in FOXO3-induced autophagy. ..
  88. Tomescu O, Xia S, Strezlecki D, Bennicelli J, Ginsberg J, Pawel B, et al. Inducible short-term and stable long-term cell culture systems reveal that the PAX3-FKHR fusion oncoprotein regulates CXCR4, PAX3, and PAX7 expression. Lab Invest. 2004;84:1060-70 pubmed
    In the pediatric cancer alveolar rhabdomyosarcoma (ARMS), the 2;13 chromosomal translocation juxtaposes the PAX3 and FKHR genes to generate a chimeric transcription factor...
  89. Dowell P, Otto T, Adi S, Lane M. Convergence of peroxisome proliferator-activated receptor gamma and Foxo1 signaling pathways. J Biol Chem. 2003;278:45485-91 pubmed
    The forkhead factor Foxo1 (or FKHR) was identified in a yeast two-hybrid screen as a peroxisome proliferator-activated receptor (PPAR) gamma-interacting protein...
  90. Chen Q, Ganapathy S, Singh K, Shankar S, Srivastava R. Resveratrol induces growth arrest and apoptosis through activation of FOXO transcription factors in prostate cancer cells. PLoS ONE. 2010;5:e15288 pubmed publisher
    ..Resveratrol has no effect on the expression of FKHR, FKHRL1 and AFX genes...