AC T02938
AS T04177.
XX
ID T02938
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DT 03.02.2000 (created); rio.
DT 05.08.2015 (updated); hna.
CO Copyright (C), QIAGEN.
XX
FA FOXO3a
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SY AF6q21; DKFZp781A0677; FKHRL1; FKHRL1P2; forkhead box O3; forkhead box O3A; FOXO2; Foxo3; FOXO3A; MGC12739; MGC31925.
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OS human, Homo sapiens
OC eukaryota; animalia; metazoa; chordata; vertebrata; tetrapoda; mammalia; eutheria; primates
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GE G004640 FOXO3; HGNC: Foxo3.
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HO daf-16 (C. elegans).
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CL C0023; fork head; 3.3.1.15.2.
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SF highest similarity to FOXO4 T03403 and FOXO1a T02936 [3];
SF 86% identical to FOXO1a T02936 [1];
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CP (adult:) brain, blood, colon, kidney, ovary, skeletal, muscle [1], T helper cells [2] [1] [2]; (adult:) heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, (cell lines:) HL60, HeLa, K562, MOLT4, Raji, SW480, A549, G361 [3]; Sympathetic neurons [7].
XX
FF translocation t(6;
FF 11)(q21;
FF q23) results in fusion with the MLL gene and causes secondary acute leukemia [3];
FF NGF regulates the phosphorylation and localizes of this protein in sympathetic neurons [7];
FF FOXO3a induces transcription of p130, thereby causing cell cycle exit [6];
FF activates basal hPDK4 expression (transcriptional activator), while insulin and PKB inhibit the function by phosphorylation;
FF may have regulatory roles in immune response [2];
FF the serine/threonine kinase Akt prevents FOXO3a dependent transcription by phosphorylation (T32, S253) [4];
FF phosphorylated FOXA3a is retained in the cytoplasm by binding to the scaffold protein 14-3-3 zeta T04390 [4];
FF triggers apoptosis by inducing the expression of genes that are critical for cell death, such as the Fas ligand gene and the Bcl-2 interacting mediator Bim [4] [5];
FF induces transcription of Retinoblastoma-like protein 2 (RBL2/p130), thereby causing cell cycle exit [6];
FF relocalizes to the nucleus upon nutrient withdrawal [8];
FF FOXO3a triple mutant, with three consensus AKT/PKB phosphorylation sites mutated to alanine (T32A, S253A, S315A), is constitutively nuclear localized and active [8];
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IN T09248 AML2-isoform1; human, Homo sapiens.
IN T02872 beta-catenin; human, Homo sapiens.
IN T00261 ER-alpha; human, Homo sapiens.
IN T02752 LXR-alpha; human, Homo sapiens.
IN T04453 LXR-beta; human, Homo sapiens.
IN T01427 p300; human, Homo sapiens.
IN T00671 p53; human, Homo sapiens.
IN T29717 SIRT1; human, Homo sapiens.
IN T04292 Smad4; human, Homo sapiens.
IN T00885 VDR; human, Homo sapiens.
XX
MX M01137 V$FOXO3A_Q1.
MX M07287 V$FOXO3A_Q3.
MX M00477 V$FOXO3_01.
MX M02270 V$FOXO3_02.
MX M04259 V$FOXO3_04.
MX M04260 V$FOXO3_05.
XX
BS R09923.
BS R09924.
BS R26191.
BS R26005.
BS R67619.
BS R28578.
BS R62423.
BS R62428.
BS R62431.
BS R69097.
BS R26007.
BS R17146.
BS R17147.
BS R67166.
BS R17152.
BS R17153.
BS R17154.
BS R26306.
BS R26308.
BS R26309.
BS R26310.
BS R39731.
BS R39732.
BS R39733.
BS R39735.
BS R39736.
BS R39737.
BS R39738.
BS R26231.
BS R12332.
BS R26361.
BS R19455.
BS R59435.
BS R62058.
BS R62059.
BS R26360.
BS R62637.
BS R62639.
BS R17223.
BS R18134.
BS R18135.
BS R26187.
BS R63273.
BS R63908.
BS R31039.
BS R38380.
BS R21500.
BS R21501.
BS R21502.
BS R28540.
BS R09922.
BS R73111.
BS R40667.
BS R63872.
BS R63877.
BS R59464.
XX
DR TRANSPATH: MO000020701.
DR EMBL: AF041336;
DR UniProtKB: O43524;
XX
RN [1]; RE0013365.
RX PUBMED: 9479491.
RA Anderson M. J., Viars C. S., Czekay S., Cavenee W. K., Arden K. C.
RT Cloning and characterization of three human forkhead genes that comprise an FKHR-like gene subfamily
RL Genomics 47:187-199 (1998).
RN [2]; RE0013367.
RX PUBMED: 9852958.
RA DaSilva L., Kirken R. A., Taub D. D., Evans G. A., Duhe R. J., Bailey M. A., Farrar W. L.
RT Molecular cloning of FKHRL1P2, a member of the developmentally regulated fork head domain transcription factor family
RL Gene 221:135-142 (1998).
RN [3]; RE0015571.
RX PUBMED: 9345057.
RA Hillion J., Le Coniat M., Jonveaux P., Berger R., Bernard O. A.
RT AF6q21, a novel partner of the MLL gene in t(6;11)(q21;q23), defines a forkhead transcriptional factor subfamily
RL Blood 90:3714-3719 (1997).
RN [4]; RE0015966.
RX PUBMED: 10102273.
RA 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.
RT Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor
RL Cell 96:857-868 (1999).
RN [5]; RE0015967.
RX PUBMED: 11050388.
RA Dijkers P. F., Medemadagger R. H., Lammers J. W., Koenderman L., Coffer P. J.
RT Expression of the pro-apoptotic Bcl-2 family member Bim is regulated by the forkhead transcription factor FKHR-L1
RL Curr. Biol. 10:1201-1204 (2000).
RN [6]; RE0017991.
RX PUBMED: 11884591.
RA Kops G. J. L., Medema R. H., Glassford J., Essers M. A., Dijkers P. F., Coffer P. J., Lam E. W.-F., Burgering B. M. T.
RT Control of cell cycle exit and entry by protein kinase B-regulated forkhead transcription factors.
RL Mol. Cell. Biol. 22:2025-2036 (2002).
RN [7]; RE0025232.
RX PUBMED: 12913110.
RA Gilley J., Coffer P. J., Ham J.
RT FOXO transcription factors directly activate bim gene expression and promote apoptosis in sympathetic neurons.
RL J. Cell Biol. 162:613-622 (2003).
RN [8]; RE0025408.
RX PUBMED: 15604409.
RA Nemoto S., Fergusson M. M., Finkel T.
RT Nutrient availability regulates SIRT1 through a forkhead-dependent pathway.
RL Science 306:2105-2108 (2004).
RN [9]; RE0030982.
RX PUBMED: 15084259.
RA Seoane J., Le H. V., Shen L., Anderson S. A., Massague J.
RT Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation.
RL Cell 117:211-23 (2004).
RN [10]; RE0032615.
RX PUBMED: 15084260.
RA Hu M. C., Lee D. F., Xia W., Golfman L. S., Ou-Yang F., Yang J. Y., Zou Y., Bao S., Hanada N., Saso H., Kobayashi R., Hung M. C.
RT IkappaB kinase promotes tumorigenesis through inhibition of forkhead FOXO3a.
RL Cell 117:225-37 (2004).
RN [11]; RE0032966.
RX PUBMED: 11953455.
RA Zheng W. H., Kar S., Quirion R.
RT FKHRL1 and its homologs are new targets of nerve growth factor Trk receptor signaling.
RL J. Neurochem 80:1049-61 (2002).
RN [12]; RE0048307.
RX PUBMED: 16373335.
RA Yamamura Y., Lee W. L., Inoue K., Ida H., Ito Y.
RT RUNX3 cooperates with FoxO3a to induce apoptosis in gastric cancer cells.
RL J. Biol. Chem. 281:5267-5276 (2006).
RN [13]; RE0051909.
RX PUBMED: 18204439.
RA Yang J. Y., Zong C. S., Xia W., Yamaguchi H., Ding Q., Xie X., Lang J. Y., Lai C. C., Chang C. J., Huang W. C., Huang H., Kuo H. P., Lee D. F., Li L. Y., Lien H. C., Cheng X., Chang K. J., Hsiao C. D., Tsai F. J., Tsai C. H., Sahin A. A., Muller W. J., Mills G. B., Yu D., Hortobagyi G. N., Hung M. C.
RT ERK promotes tumorigenesis by inhibiting FOXO3a via MDM2-mediated degradation.
RL Nat. Cell Biol. 10:138-148 (2008).
RN [14]; RE0053798.
RX PUBMED: 18458087.
RA Allard D., Figg N., Bennett M. R., Littlewood T. D.
RT Akt Regulates the Survival of Vascular Smooth Muscle Cells via Inhibition of FoxO3a and GSK3.
RL J. Biol. Chem. 283:19739-19747 (2008).
RN [15]; RE0054989.
RX PUBMED: 15604093.
RA Albers M., Kranz H., Kober I., Kaiser C., Klink M., Suckow J., Kern R., Koegl M.
RT Automated yeast two-hybrid screening for nuclear receptor-interacting proteins.
RL Mol. Cell. Proteomics 4:205-213 (2005).
RN [16]; RE0055067.
RX PUBMED: 18593906.
RA Morishita D., Katayama R., Sekimizu K., Tsuruo T., Fujita N.
RT Pim kinases promote cell cycle progression by phosphorylating and down-regulating p27Kip1 at the transcriptional and posttranscriptional levels.
RL Cancer Res. 68:5076-5085 (2008).
RN [17]; RE0055951.
RX PUBMED: 17726016.
RA Jang S. W., Yang S. J., Srinivasan S., Ye K.
RT Akt phosphorylates MstI and prevents its proteolytic activation, blocking FOXO3 phosphorylation and nuclear translocation.
RL J. Biol. Chem. 282:30836-30844 (2007).
RN [18]; RE0063662.
RX PUBMED: 19473970.
RA Ding B., Kirkiles-Smith N. C., Pober J. S.
RT FOXO3a regulates oxygen-responsive expression of tumor necrosis factor receptor 2 in human dermal microvascular endothelial cells.
RL J. Biol. Chem. 284:19331-19339 (2009).
RN [19]; RE0066672.
RX PUBMED: 15620712.
RA Rosas M., Birkenkamp K. U., Lammers J. W., Koenderman L., Coffer P. J.
RT Cytokine mediated suppression of TF-1 apoptosis requires PI3K activation and inhibition of Bim expression.
RL FEBS Lett. 579:191-198 (2005).
RN [20]; RE0067981.
RX PUBMED: 18678662.
RA Snoeks L., Weber C. R., Turner J. R., Bhattacharyya M., Wasland K., Savkovic S. D.
RT Tumor suppressor Foxo3a is involved in the regulation of lipopolysaccharide-induced interleukin-8 in intestinal HT-29 cells.
RL Infect. Immun. 76:4677-4685 (2008).
RN [21]; RE0068370.
RX PUBMED: 18499891.
RA Oostendorp R. A., Gilfillan S., Parmar A., Schiemann M., Marz S., Niemeyer M., Schill S., Hammerschmid E., Jacobs V. R., Peschel C., Gotze K. S.
RT Oncostatin M-mediated regulation of KIT-ligand-induced extracellular signal-regulated kinase signaling maintains hematopoietic repopulating activity of Lin-CD34+CD133+ cord blood cells.
RL Stem Cells 26:2164-2172 (2008).
RN [22]; RE0069409.
RX PUBMED: 18344987.
RA Tsai W. B., Chung Y. M., Takahashi Y., Xu Z., Hu M. C.
RT Functional interaction between FOXO3a and ATM regulates DNA damage response.
RL Nat. Cell Biol. 10:460-467 (2008).
RN [23]; RE0070207.
RX PUBMED: 20733005.
RA An B. S., Tavera-Mendoza L. E., Dimitrov V., Wang X., Calderon M. R., Wang H. J., White J. H.
RT Stimulation of Sirt1-regulated FoxO protein function by the ligand-bound vitamin D receptor.
RL Mol. Cell. Biol. 30:4890-4900 (2010).
RN [24]; RE0070735.
RX PUBMED: 20110348.
RA Singh A., Ye M., Bucur O., Zhu S., Tanya Santos M., Rabinovitz I., Wei W., Gao D., Hahn W. C., Khosravi-Far R.
RT Protein phosphatase 2A reactivates FOXO3a through a dynamic interplay with 14-3-3 and AKT.
RL Mol. Biol. Cell 21:1140-1152 (2010).
RN [25]; RE0071525.
RX PUBMED: 18385518.
RA Chahdi A., Sorokin A.
RT Endothelin-1 couples betaPix to p66Shc: role of betaPix in cell proliferation through FOXO3a phosphorylation and p27kip1 down-regulation independently of Akt.
RL Mol. Biol. Cell 19:2609-2619 (2008).
RN [26]; RE0071546.
RX PUBMED: 21965295.
RA Diebold I., Petry A., Burger M., Hess J., Gorlach A.
RT NOX4 mediates activation of FoxO3a and matrix metalloproteinase-2 expression by urotensin-II.
RL Mol. Biol. Cell 22:4424-4434 (2011).
RN [27]; RE0071936.
RX PUBMED: 15905404.
RA Essers M. A., de Vries-Smits L. M., Barker N., Polderman P. E., Burgering B. M., Korswagen H. C.
RT Functional interaction between beta-catenin and FOXO in oxidative stress signaling.
RL Science 308:1181-1184 (2005).
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