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Gene Review

FOXO3  -  forkhead box O3

Homo sapiens

Synonyms: AF6q21, AF6q21 protein, FKHRL1, FKHRL1P2, FOXO2, ...
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Disease relevance of FOXO3


High impact information on FOXO3


Chemical compound and disease context of FOXO3


Biological context of FOXO3


Anatomical context of FOXO3


Associations of FOXO3 with chemical compounds


Enzymatic interactions of FOXO3

  • Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a) [12].
  • We show that AMPK phosphorylates human FOXO3 at six previously unidentified regulatory sites [22].

Regulatory relationships of FOXO3

  • Forkhead factor FKHRL1 binds in vitro to the three consensus sequences and can activate TGF-beta2 promoter in normal and Akt-transformed cell lines [23].
  • A member of Forkhead transcription factor FKHRL1 is a downstream effector of STI571-induced cell cycle arrest in BCR-ABL-expressing cells [21].
  • RESULTS: We demonstrate that Hcy induces dephosphorylation of Akt and FKHRL1 and upregulates the cyclin-dependent kinase inhibitors p27(kip1) in a time- and dose-dependent manner [24].
  • In addition, Epo treatment of erythroid progenitors induces phosphorylation of a member of the Forkhead family (FH) of transcription factors FKHRL1, downstream of activation of the Akt kinase [25].
  • Similarly, induction of FasL by the Akt-regulated forkhead transcription factor FKHRL1 was dependent upon caspase and c-Jun activation [26].

Other interactions of FOXO3


Analytical, diagnostic and therapeutic context of FOXO3


  1. FOXO proteins regulate tumor necrosis factor-related apoptosis inducing ligand expression. Implications for PTEN mutation in prostate cancer. Modur, V., Nagarajan, R., Evers, B.M., Milbrandt, J. J. Biol. Chem. (2002) [Pubmed]
  2. How does the human RUNX3 gene induce apoptosis in gastric cancer? Latest data, reflections and reactions. Vogiatzi, P., De Falco, G., Claudio, P.P., Giordano, A. Cancer Biol. Ther. (2006) [Pubmed]
  3. Subcellular localisation of Cdc25A determines cell fate. Leisser, C., Rosenberger, G., Maier, S., Fuhrmann, G., Grusch, M., Strasser, S., Huettenbrenner, S., Fassl, S., Polgar, D., Krieger, S., Cerni, C., Hofer-Warbinek, R., deMartin, R., Krupitza, G. Cell Death Differ. (2004) [Pubmed]
  4. Ionizing radiation activates expression of FOXO3a, Fas ligand, and Bim, and induces cell apoptosis. Yang, J.Y., Xia, W., Hu, M.C. Int. J. Oncol. (2006) [Pubmed]
  5. Expression and intracellular localization of FKHRL1 in mammary gland neoplasms. Jin, G.S., Kondo, E., Miyake, T., Shibata, M., Takashima, T., Liu, Y.X., Hayashi, K., Akagi, T., Yoshino, T. Acta Med. Okayama (2004) [Pubmed]
  6. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Brunet, A., Bonni, A., Zigmond, M.J., Lin, M.Z., Juo, P., Hu, L.S., Anderson, M.J., Arden, K.C., Blenis, J., Greenberg, M.E. Cell (1999) [Pubmed]
  7. Convergence of TCR and cytokine signaling leads to FOXO3a phosphorylation and drives the survival of CD4+ central memory T cells. Riou, C., Yassine-Diab, B., Van Grevenynghe, J., Somogyi, R., Greller, L.D., Gagnon, D., Gimmig, S., Wilkinson, P., Shi, Y., Cameron, M.J., Campos-Gonzalez, R., Balderas, R.S., Kelvin, D., Sekaly, R.P., Haddad, E.K. J. Exp. Med. (2007) [Pubmed]
  8. Bim regulation may determine hippocampal vulnerability after injurious seizures and in temporal lobe epilepsy. Shinoda, S., Schindler, C.K., Meller, R., So, N.K., Araki, T., Yamamoto, A., Lan, J.Q., Taki, W., Simon, R.P., Henshall, D.C. J. Clin. Invest. (2004) [Pubmed]
  9. 14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport. Brunet, A., Kanai, F., Stehn, J., Xu, J., Sarbassova, D., Frangioni, J.V., Dalal, S.N., DeCaprio, J.A., Greenberg, M.E., Yaffe, M.B. J. Cell Biol. (2002) [Pubmed]
  10. Inhibition of phosphorylation of a forkhead transcription factor sensitizes human ovarian cancer cells to cisplatin. Arimoto-Ishida, E., Ohmichi, M., Mabuchi, S., Takahashi, T., Ohshima, C., Hayakawa, J., Kimura, A., Takahashi, K., Nishio, Y., Sakata, M., Kurachi, H., Tasaka, K., Murata, Y. Endocrinology (2004) [Pubmed]
  11. Induction of apoptosis by L-NMMA, via FKHRL1/ROCK pathway in human gastric cancer cells. Wang, Y.Z., Feng, Z.Q. Biomed. Environ. Sci. (2006) [Pubmed]
  12. Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a). Brunet, A., Park, J., Tran, H., Hu, L.S., Hemmings, B.A., Greenberg, M.E. Mol. Cell. Biol. (2001) [Pubmed]
  13. MUC1 oncoprotein activates the FOXO3a transcription factor in a survival response to oxidative stress. Yin, L., Huang, L., Kufe, D. J. Biol. Chem. (2004) [Pubmed]
  14. Insulin-like growth factor-I induces the phosphorylation and nuclear exclusion of forkhead transcription factors in human neuroblastoma cells. Schwab, T.S., Madison, B.B., Grauman, A.R., Feldman, E.L. Apoptosis (2005) [Pubmed]
  15. Selenium sensitizes MCF-7 breast cancer cells to doxorubicin-induced apoptosis through modulation of phospho-Akt and its downstream substrates. Li, S., Zhou, Y., Wang, R., Zhang, H., Dong, Y., Ip, C. Mol. Cancer Ther. (2007) [Pubmed]
  16. A member of Forkhead family transcription factor, FKHRL1, is one of the downstream molecules of phosphatidylinositol 3-kinase-Akt activation pathway in erythropoietin signal transduction. Kashii, Y., Uchida, M., Kirito, K., Tanaka, M., Nishijima, K., Toshima, M., Ando, T., Koizumi, K., Endoh, T., Sawada, K., Momoi, M., Miura, Y., Ozawa, K., Komatsu, N. Blood (2000) [Pubmed]
  17. Proteolytic regulation of Forkhead transcription factor FOXO3a by caspase-3-like proteases. Charvet, C., Alberti, I., Luciano, F., Jacquel, A., Bernard, A., Auberger, P., Deckert, M. Oncogene (2003) [Pubmed]
  18. Loss of PTEN/MMAC1/TEP in EGF receptor-expressing tumor cells counteracts the antitumor action of EGFR tyrosine kinase inhibitors. Bianco, R., Shin, I., Ritter, C.A., Yakes, F.M., Basso, A., Rosen, N., Tsurutani, J., Dennis, P.A., Mills, G.B., Arteaga, C.L. Oncogene (2003) [Pubmed]
  19. FKHRL1 and its homologs are new targets of nerve growth factor Trk receptor signaling. Zheng, W.H., Kar, S., Quirion, R. J. Neurochem. (2002) [Pubmed]
  20. Molecular cloning of FKHRL1P2, a member of the developmentally regulated fork head domain transcription factor family. DaSilva, L., Kirken, R.A., Taub, D.D., Evans, G.A., Duhé, R.J., Bailey, M.A., Farrar, W.L. Gene (1998) [Pubmed]
  21. A member of Forkhead transcription factor FKHRL1 is a downstream effector of STI571-induced cell cycle arrest in BCR-ABL-expressing cells. Komatsu, N., Watanabe, T., Uchida, M., Mori, M., Kirito, K., Kikuchi, S., Liu, Q., Tauchi, T., Miyazawa, K., Endo, H., Nagai, T., Ozawa, K. J. Biol. Chem. (2003) [Pubmed]
  22. The energy sensor AMP-activated protein kinase directly regulates the mammalian FOXO3 transcription factor. Greer, E.L., Oskoui, P.R., Banko, M.R., Maniar, J.M., Gygi, M.P., Gygi, S.P., Brunet, A. J. Biol. Chem. (2007) [Pubmed]
  23. Transforming growth factor-beta 2 is a transcriptional target for Akt/protein kinase B via forkhead transcription factor. Samatar, A.A., Wang, L., Mirza, A., Koseoglu, S., Liu, S., Kumar, C.C. J. Biol. Chem. (2002) [Pubmed]
  24. Homocysteine induces cell cycle G1 arrest in endothelial cells through the PI3K/Akt/FOXO signaling pathway. Zhang, H.S., Cao, E.H., Qin, J.F. Pharmacology (2005) [Pubmed]
  25. Activation of the Akt/FKHRL1 pathway mediates the antiapoptotic effects of erythropoietin in primary human erythroid progenitors. Uddin, S., Kottegoda, S., Stigger, D., Platanias, L.C., Wickrema, A. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  26. Suppression of Akt signaling induces Fas ligand expression: involvement of caspase and Jun kinase activation in Akt-mediated Fas ligand regulation. Suhara, T., Kim, H.S., Kirshenbaum, L.A., Walsh, K. Mol. Cell. Biol. (2002) [Pubmed]
  27. Cloning and characterization of three human forkhead genes that comprise an FKHR-like gene subfamily. Anderson, M.J., Viars, C.S., Czekay, S., Cavenee, W.K., Arden, K.C. Genomics (1998) [Pubmed]
  28. AF6q21, a novel partner of the MLL gene in t(6;11)(q21;q23), defines a forkhead transcriptional factor subfamily. Hillion, J., Le Coniat, M., Jonveaux, P., Berger, R., Bernard, O.A. Blood (1997) [Pubmed]
  29. Ligand-dependent interaction of estrogen receptor-alpha with members of the forkhead transcription factor family. Schuur, E.R., Loktev, A.V., Sharma, M., Sun, Z., Roth, R.A., Weigel, R.J. J. Biol. Chem. (2001) [Pubmed]
  30. FKHRL1-mediated expression of Noxa and Bim induces apoptosis via the mitochondria in neuroblastoma cells. Obexer, P., Geiger, K., Ambros, P.F., Meister, B., Ausserlechner, M.J. Cell Death Differ. (2007) [Pubmed]
  31. Activated forkhead transcription factor inhibits neointimal hyperplasia after angioplasty through induction of p27. Park, K.W., Kim, D.H., You, H.J., Sir, J.J., Jeon, S.I., Youn, S.W., Yang, H.M., Skurk, C., Park, Y.B., Walsh, K., Kim, H.S. Arterioscler. Thromb. Vasc. Biol. (2005) [Pubmed]
  32. Mechanisms of the apoptotic activity of Cl-F-araA in a human T-ALL cell line, CCRF-CEM. Takahashi, T., Shimizu, M., Akinaga, S. Cancer Chemother. Pharmacol. (2002) [Pubmed]
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