Gene Symbol: Foxo3
Description: forkhead box O3
Alias: Fkhrl1, Foxo3a, forkhead box protein O3, forkhead box O3a
Species: rat
Products:     Foxo3

Top Publications

  1. Tran H, Brunet A, Grenier J, Datta S, Fornace A, DiStefano P, et al. DNA repair pathway stimulated by the forkhead transcription factor FOXO3a through the Gadd45 protein. Science. 2002;296:530-4 pubmed
    ..We show that mammalian FOXO3a also functions at the G2 to M checkpoint in the cell cycle and triggers the repair of damaged DNA...
  2. Andreucci M, Michael A, Kramers C, Park K, Chen A, Matthaeus T, et al. Renal ischemia/reperfusion and ATP depletion/repletion in LLC-PK(1) cells result in phosphorylation of FKHR and FKHRL1. Kidney Int. 2003;64:1189-98 pubmed
    ..anoxia followed by dextrose addition for 20 minutes to replete adenosine triphosphate (ATP) levels, FKHR and FKHRL1 are phosphorylated...
  3. Sengupta A, Molkentin J, Yutzey K. FoxO transcription factors promote autophagy in cardiomyocytes. J Biol Chem. 2009;284:28319-31 pubmed publisher
    ..Likewise, overexpression of either FoxO1 or FoxO3 reduces cardiomyocyte cell size and induces expression of autophagy pathway genes...
  4. Brunet A, Bonni A, Zigmond M, Lin M, Juo P, Hu L, et al. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 1999;96:857-68 pubmed
    ..In this study, we demonstrate that Akt also regulates the activity of FKHRL1, a member of the Forkhead family of transcription factors...
  5. Lu D, Liu J, Jiao J, Long B, Li Q, Tan W, et al. Transcription factor Foxo3a prevents apoptosis by regulating calcium through the apoptosis repressor with caspase recruitment domain. J Biol Chem. 2013;288:8491-504 pubmed publisher
    ..The forkhead family of transcription factor Foxo3a plays a pivotal role in apoptosis; however, its role in regulating cardiac apoptosis remains to be fully ..
  6. Elia L, Contu R, Quintavalle M, Varrone F, Chimenti C, Russo M, et al. Reciprocal regulation of microRNA-1 and insulin-like growth factor-1 signal transduction cascade in cardiac and skeletal muscle in physiological and pathological conditions. Circulation. 2009;120:2377-85 pubmed publisher
    ..the activation state of the IGF-1 signal transduction cascade reciprocally regulates miR-1 expression through the Foxo3a transcription factor; and (4) miR-1 expression correlates inversely with cardiac mass and thickness in myocardial ..
  7. Castrillon D, Miao L, Kollipara R, Horner J, Depinho R. Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a. Science. 2003;301:215-8 pubmed
    ..Here, we show that Foxo3a-/- female mice exhibit a distinctive ovarian phenotype of global follicular activation leading to oocyte death, ..
  8. Vahtola E, Louhelainen M, Merasto S, Martonen E, Penttinen S, Aahos I, et al. Forkhead class O transcription factor 3a activation and Sirtuin1 overexpression in the hypertrophied myocardium of the diabetic Goto-Kakizaki rat. J Hypertens. 2008;26:334-44 pubmed publisher
    ..The proapoptotic forkhead class O transcription factor 3a (FOXO3a) and its modulator, the cardioprotective longevity factor and class III histone deacetylase Sirtuin1 (Sirt1), have ..
  9. Lehtinen M, Yuan Z, Boag P, Yang Y, Villen J, Becker E, et al. A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. Cell. 2006;125:987-1001 pubmed

More Information


  1. Wang K, Li P. Foxo3a regulates apoptosis by negatively targeting miR-21. J Biol Chem. 2010;285:16958-66 pubmed publisher
    ..Here we report that the transcriptional factor Foxo3a initiates apoptosis by transcriptionally repressing miR-21 expression...
  2. Vahtola E, Louhelainen M, Forsten H, Merasto S, Raivio J, Kaheinen P, et al. Sirtuin1-p53, forkhead box O3a, p38 and post-infarct cardiac remodeling in the spontaneously diabetic Goto-Kakizaki rat. Cardiovasc Diabetol. 2010;9:5 pubmed publisher
    ..Goto Kakizaki rats as a model of type 2 DM we investigated whether post-translational modifications in the Akt - FOXO3a pathway, Sirt1 - p53 pathway and the mitogen activated protein kinase p38 regulator are involved in post-infarct ..
  3. Jacobs F, van der Heide L, Wijchers P, Burbach J, Hoekman M, Smidt M. FoxO6, a novel member of the FoxO class of transcription factors with distinct shuttling dynamics. J Biol Chem. 2003;278:35959-67 pubmed
    ..after stimulation with growth factors, in contrast to the predominant cytosolic localization of FoxO1 and FoxO3. We also show that nuclear export of FoxO6 is mediated through the phosphatidylinositol 3-kinase/PKB pathway...
  4. Essers M, de Vries Smits L, Barker N, Polderman P, Burgering B, Korswagen H. Functional interaction between beta-catenin and FOXO in oxidative stress signaling. Science. 2005;308:1181-4 pubmed
    ..These results demonstrate a role for beta-catenin in regulating FOXO function that is particularly important under conditions of oxidative stress. ..
  5. Tan W, Wang K, Lv D, Li P. Foxo3a inhibits cardiomyocyte hypertrophy through transactivating catalase. J Biol Chem. 2008;283:29730-9 pubmed publisher
    The forkhead transcription factor Foxo3a is able to inhibit cardiomyocyte hypertrophy. However, its underlying molecular mechanism remains to be fully understood...
  6. Caballero Caballero A, Engel T, Martínez Villarreal J, Sanz Rodriguez A, Chang P, Dunleavy M, et al. Mitochondrial localization of the forkhead box class O transcription factor FOXO3a in brain. J Neurochem. 2013;124:749-56 pubmed publisher
    b>FOXO3a is member of the Forkhead box class O transcription factors, which functions in diverse pathways to regulate cellular metabolism, differentiation, and apoptosis...
  7. Chen Y, Lai Y, Lin S, Li X, Fu Y, Xu W. SIRT1 interacts with metabolic transcriptional factors in the pancreas of insulin-resistant and calorie-restricted rats. Mol Biol Rep. 2013;40:3373-80 pubmed publisher
    ..of glucose and fat homeostasis by regulating transcription factors such as forkhead transcription factor 3a (FOXO3a), glucose transporter 4 (GLUT4), peroxisome proliferator-activated receptor gamma (PPAR?) and PPAR? coactivator (..
  8. Wang H, Duan X, Ren Y, Liu Y, Huang M, Liu P, et al. FoxO3a negatively regulates nerve growth factor-induced neuronal differentiation through inhibiting the expression of neurochondrin in PC12 cells. Mol Neurobiol. 2013;47:24-36 pubmed publisher
    Forkhead box O3 (FoxO3a) is a forkhead family transcription factor playing important roles in non-neuronal differentiation, metabolism, proliferation, and survival, but its role in neuronal differentiation remains unclear...
  9. Westin S, Ju Z, Broaddus R, Krakstad C, Li J, Pal N, et al. PTEN loss is a context-dependent outcome determinant in obese and non-obese endometrioid endometrial cancer patients. Mol Oncol. 2015;9:1694-703 pubmed publisher
    ..was observed only in the non-obese population while decreased expression of β-CATENIN and phosphorylated FOXO3A was observed in obese patients...
  10. Jeong H, Jeong H, Song S, Kang J, Seo J, Lee Y, et al. Upregulation of peroxiredeoxin III in the hippocampus of acute immobilization stress model rats and the Foxo3a-dependent expression in PC12 cells. Cell Mol Neurobiol. 2011;31:1041-6 pubmed publisher
    ..In addition, we tested whether the transcription factor Foxo3a was necessary for the expression of Prx III...
  11. Wang X, Chen L, Maures T, Herrington J, Carter Su C. SH2-B is a positive regulator of nerve growth factor-mediated activation of the Akt/Forkhead pathway in PC12 cells. J Biol Chem. 2004;279:133-41 pubmed
    ..of the pro-apoptotic Akt effector proteins, glycogen synthase kinase-3, and forkhead transcription factors, FKHRL1/FOXO3 and FKHR/FOXO1...
  12. Paik J, Ding Z, Narurkar R, Ramkissoon S, Muller F, Kamoun W, et al. FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis. Cell Stem Cell. 2009;5:540-53 pubmed publisher
    ..Thus, the FoxO family coordinately regulates diverse genes and pathways to govern key aspects of NSC homeostasis in the mammalian brain. ..
  13. Imae M, Fu Z, Yoshida A, Noguchi T, Kato H. Nutritional and hormonal factors control the gene expression of FoxOs, the mammalian homologues of DAF-16. J Mol Endocrinol. 2003;30:253-62 pubmed
    ..Three members of this family have been identified in rodents: FoxO1, FoxO3 and FoxO4, originally termed FKHR, FKHRL1 and AFX respectively...
  14. Hou J, Chong Z, Shang Y, Maiese K. FOXO3a governs early and late apoptotic endothelial programs during elevated glucose through mitochondrial and caspase signaling. Mol Cell Endocrinol. 2010;321:194-206 pubmed publisher
    ..that Akt1 and the post-translational modification and subcellular trafficking of the forkhead transcription factor FoxO3a are critical for early apoptotic membrane signaling and subsequent degradation of nuclear DNA...
  15. Guo J, Gertsberg Z, Ozgen N, Steinberg S. p66Shc links alpha1-adrenergic receptors to a reactive oxygen species-dependent AKT-FOXO3A phosphorylation pathway in cardiomyocytes. Circ Res. 2009;104:660-9 pubmed publisher
    ..pathway that requires the cooperative effects of protein kinase (PK)Cepsilon and PKCdelta and leads to AKT-FOXO3a phosphorylation in cardiomyocytes...
  16. Mounier C, Dumas V, Posner B. Regulation of hepatic insulin-like growth factor-binding protein-1 gene expression by insulin: central role for mammalian target of rapamycin independent of forkhead box O proteins. Endocrinology. 2006;147:2383-91 pubmed
    ..protein kinase B (Akt), phosphorylation of the transcription factors forkhead in rhabdomyosarcoma 1 (Foxo1)/Foxo3, and the mammalian target of rapamycin (mTOR) in insulin's effect...
  17. Kato M, Yuan H, Xu Z, Lanting L, Li S, Wang M, et al. Role of the Akt/FoxO3a pathway in TGF-beta1-mediated mesangial cell dysfunction: a novel mechanism related to diabetic kidney disease. J Am Soc Nephrol. 2006;17:3325-35 pubmed
    ..We tested whether phosphorylation-mediated inactivation of FoxO3a by TGF-beta can mediate MC survival and oxidative stress...
  18. Wilk A, Urbanska K, Yang S, Wang J, Amini S, Del Valle L, et al. Insulin-like growth factor-I-forkhead box O transcription factor 3a counteracts high glucose/tumor necrosis factor-?-mediated neuronal damage: implications for human immunodeficiency virus encephalitis. J Neurosci Res. 2011;89:183-98 pubmed publisher
    ..Because mammalian homolog of the Forkhead family of transcription factors, Forkhead box O transcription factor 3a (FOXO3a), controls ROS metabolism, we asked whether FOXO3a could affect the fate of differentiated neurons in the paradigm ..
  19. Pramod S, Shivakumar K. Mechanisms in cardiac fibroblast growth: an obligate role for Skp2 and FOXO3a in ERK1/2 MAPK-dependent regulation of p27kip1. Am J Physiol Heart Circ Physiol. 2014;306:H844-55 pubmed publisher
    ..of p27(Kip1) mRNA in ERK1/2-inhibited cells, demonstrated by real-time PCR, correlated with forkhead box O 3a (FOXO3a) transcription factor activation, shown by gel shift assay...
  20. Lu J, Zhang R, Hong H, Yang Z, Sun D, Sun S, et al. The poly(ADP-ribosyl)ation of FoxO3 mediated by PARP1 participates in isoproterenol-induced cardiac hypertrophy. Biochim Biophys Acta. 2016;1863:3027-3039 pubmed publisher
    The Forkhead box-containing protein, O subfamily 3 (FoxO3) transcription factor negatively regulates myocardial hypertrophy, and its transcriptional activity is finely conditioned by diverse posttranslational modifications, such as ..
  21. Sharma V, Parsons H, Allard M, McNeill J. Metoprolol increases the expression of beta(3)-adrenoceptors in the diabetic heart: effects on nitric oxide signaling and forkhead transcription factor-3. Eur J Pharmacol. 2008;595:44-51 pubmed publisher
    ..beta-adrenoceptor signaling shifted from PKA to Akt-mediated signaling, associated with phosphorylation of FOXO-3 but not eNOS. ..
  22. Sun L, Zang W, Wang H, Zhao M, Yu X, He X, et al. Acetylcholine promotes ROS detoxification against hypoxia/reoxygenation-induced oxidative stress through FoxO3a/PGC-1α dependent superoxide dismutase. Cell Physiol Biochem. 2014;34:1614-25 pubmed publisher
    ..proliferator activated receptor γ co-activator 1α (PGC-1α) and decreased forkhead box subfamily O3a (FoxO3a) phosphorylation. Atropine (muscarinic receptor antagonist) abolished the cytoprotection afforded by ACh...
  23. Wang Q, Wang Y, Zhou Z, Lu X, Cao Y, Liu Y, et al. Expressions of forkhead class box O 3a on crushed rat sciatic nerves and differentiated primary Schwann cells. Cell Mol Neurobiol. 2011;31:509-18 pubmed publisher
    Forkhead box-containing protein, class O 3 a (FOXO3a), an Akt downstream target, plays an important role in peripheral nervous system...
  24. Wang X, Wang X, Tong M, Gan L, Chen H, Wu S, et al. SIRT6 protects cardiomyocytes against ischemia/reperfusion injury by augmenting FoxO3α-dependent antioxidant defense mechanisms. Basic Res Cardiol. 2016;111:13 pubmed publisher
    ..AMP/ATP and then activate the adenosine 5'-monophosphate-activated protein kinase (AMPK)-forkhead box O3α (FoxO3α) axis and further initiated the downstream antioxidant-encoding gene expression (manganese superoxide ..
  25. Martínez Gac L, Marqués M, García Z, Campanero M, Carrera A. Control of cyclin G2 mRNA expression by forkhead transcription factors: novel mechanism for cell cycle control by phosphoinositide 3-kinase and forkhead. Mol Cell Biol. 2004;24:2181-9 pubmed
    ..We show that active forms of the forkhead transcription factor FoxO3a (FKHRL1) increase cyclin G2 mRNA levels...
  26. Li D, Qu Y, Li J, Zhang L, Xiong T, Mu D. [Role of the FOXO3a transcription factor in neuronal apoptosis in neonatal rats with hypoxic-ischemic brain damage]. Zhongguo Dang Dai Er Ke Za Zhi. 2013;15:1023-7 pubmed
    To explore the role and mechanisms of FOXO3a nuclear translocation in neuronal apoptosis after hypoxia-ischemia (HI). One hundred and sixty 10-day-old Sprague-Dawly rats were randomly divided into two groups: HI and sham-operated...
  27. Turrel Davin F, Tournadre A, Pachot A, Arnaud B, Cazalis M, Mougin B, et al. FoxO3a involved in neutrophil and T cell survival is overexpressed in rheumatoid blood and synovial tissue. Ann Rheum Dis. 2010;69:755-60 pubmed publisher
    b>FoxO3a is a transcriptional factor implicated in cell cycle regulation and apoptosis...
  28. Wang N, Zimmerman K, Raab R, McKown R, Hutnik C, Talla V, et al. Lacritin rescues stressed epithelia via rapid forkhead box O3 (FOXO3)-associated autophagy that restores metabolism. J Biol Chem. 2013;288:18146-61 pubmed publisher
    ..Accelerated flux appears to be derived from lacritin-stimulated acetylation of FOXO3 as a novel ligand for ATG101 and coupling of stress-acetylated FOXO1 with ATG7 (which remains uncoupled without ..
  29. Cho S, Cho M, Kim J, Kaeberlein M, Lee S, Suh Y. Syringaresinol protects against hypoxia/reoxygenation-induced cardiomyocytes injury and death by destabilization of HIF-1α in a FOXO3-dependent mechanism. Oncotarget. 2015;6:43-55 pubmed
    ..Knock-down of FOXO3 by specific siRNAs completely abolished the ability of syringaresinol to inhibit HIF-1 stabilization and apoptosis ..
  30. Chong Z, Hou J, Shang Y, Wang S, Maiese K. EPO relies upon novel signaling of Wnt1 that requires Akt1, FoxO3a, GSK-3?, and ?-catenin to foster vascular integrity during experimental diabetes. Curr Neurovasc Res. 2011;8:103-20 pubmed
    ..Wnt1 dependent mechanism controls the post-translational phosphorylation of the "pro-apoptotic" forkhead member FoxO3a and blocks the trafficking of FoxO3a to the cell nucleus to prevent apoptotic demise...
  31. Morishita D, Katayama R, Sekimizu K, Tsuruo T, Fujita N. Pim kinases promote cell cycle progression by phosphorylating and down-regulating p27Kip1 at the transcriptional and posttranscriptional levels. Cancer Res. 2008;68:5076-85 pubmed publisher
    ..Pim-mediated phosphorylation and inactivation of forkhead transcription factors, FoxO1a and FoxO3a, was involved in the transcriptional repression of the p27(Kip1) gene...
  32. Huang P, Zhou Z, Zheng M, Shi F. Effect of the IGF-1/PTEN/Akt/FoxO signaling pathway in the duodenal mucosa of rats subjected to water immersion and restraint stress. Genet Mol Res. 2012;11:4775-88 pubmed publisher
    ..In addition, total Akt was found in the cellular cytoplasm of the myenteric plexus. FoxO3a and FoxO4 were primarily concentrated in the cellular cytoplasm of the lamina propria...
  33. Cai B, Xia Z. p38 MAP kinase mediates arsenite-induced apoptosis through FOXO3a activation and induction of Bim transcription. Apoptosis. 2008;13:803-10 pubmed publisher
    ..Sodium arsenite also caused nuclear translocation of FOXO3a, indicative of FOXO3a activation. Addition of a p38 inhibitor prevented FOXO3a nuclear translocation...
  34. Hauck L, Harms C, Grothe D, An J, Gertz K, Kronenberg G, et al. Critical role for FoxO3a-dependent regulation of p21CIP1/WAF1 in response to statin signaling in cardiac myocytes. Circ Res. 2007;100:50-60 pubmed
    ..Lovastatin specifically recruits the forkhead box FoxO3a transcription factor to the p21 promoter, mediating transcriptional transactivation of the p21 gene as analyzed in ..
  35. Mason J, Xuan S, Dragatsis I, Efstratiadis A, Goldman J. Insulin-like growth factor (IGF) signaling through type 1 IGF receptor plays an important role in remyelination. J Neurosci. 2003;23:7710-8 pubmed
  36. Guan X, Liu X, Hong X, Zhao N, Xiao Y, Wang L, et al. CD38 Deficiency Protects the Heart from Ischemia/Reperfusion Injury through Activating SIRT1/FOXOs-Mediated Antioxidative Stress Pathway. Oxid Med Cell Longev. 2016;2016:7410257 pubmed publisher
    ..The FOXO1 and FOXO3 expressions were significantly elevated by H/R injury in CD38 knockdown cells compared with normal H9c2 cells...
  37. Li X, Du N, Zhang Q, Li J, Chen X, Liu X, et al. MicroRNA-30d regulates cardiomyocyte pyroptosis by directly targeting foxo3a in diabetic cardiomyopathy. Cell Death Dis. 2014;5:e1479 pubmed publisher
    ..Moreover, mir-30d directly repressed foxo3a expression and its downstream protein, apoptosis repressor with caspase recruitment domain (ARC)...
  38. Chen B, Wu Q, Xiong Z, Ma Y, Yu S, Chen D, et al. Adenosine monophosphate-activated protein kinase attenuates cardiomyocyte hypertrophy through regulation of FOXO3a/MAFbx signaling pathway. Acta Biochim Biophys Sin (Shanghai). 2016;48:827-32 pubmed publisher
    ..Recent studies have demonstrated that atrophy-related forkhead box O 3a (FOXO3a)/muscle atrophy F-box (MAFbx) signaling pathway plays a central role in the modulation of proteolysis and exert ..
  39. Zheng W, Kar S, Quirion R. Insulin-like growth factor-1-induced phosphorylation of transcription factor FKHRL1 is mediated by phosphatidylinositol 3-kinase/Akt kinase and role of this pathway in insulin-like growth factor-1-induced survival of cultured hippocampal neurons. Mol Pharmacol. 2002;62:225-33 pubmed
    ..b>FKHRL1, a member of the Forkhead family of transcription factors possibly involved in cell cycle and apoptosis, is a ..
  40. Laatikainen L, Incoronato M, Castellone M, Laurila J, Santoro M, Laukkanen M. SOD3 decreases ischemic injury derived apoptosis through phosphorylation of Erk1/2, Akt, and FoxO3a. PLoS ONE. 2011;6:e24456 pubmed publisher
    ..The common downstream factor of both signaling pathways, the apoptosis related forkhead box protein O3a (FoxO3a), was phosphorylated and translocated to the cytoplasm in sod3 treated tissues and cell line...
  41. Ghosh A, Klocke B, Ballestas M, Roth K. CHOP potentially co-operates with FOXO3a in neuronal cells to regulate PUMA and BIM expression in response to ER stress. PLoS ONE. 2012;7:e39586 pubmed publisher
    ..We further show that CHOP knockdown prevents perturbations in the AKT (protein kinase B)/FOXO3a (forkhead box, class O, 3a) pathway in response to ER stress...
  42. Wen Q, Duan X, Liao R, Little P, Gao G, Jiang H, et al. Characterization of intracellular translocation of Forkhead transcription factor O (FoxO) members induced by NGF in PC12 cells. Neurosci Lett. 2011;498:31-6 pubmed publisher
    ..We examined the effects of nerve growth factor (NGF) on nuclear/cytoplasmic shuttling of FoxO1, FoxO3a and FoxO6 in PC12 cells and determined their translocation kinetics...
  43. Huang C, Gu H, Zhang W, Herrmann J, Wang M. Testosterone-down-regulated Akt pathway during cardiac ischemia/reperfusion: a mechanism involving BAD, Bcl-2 and FOXO3a. J Surg Res. 2010;164:e1-11 pubmed publisher male hearts; (2) endogenous testosterone will mediate downstream signals of Akt, including Bad, Bcl-2, and FOXO3a; (3) administration of exogenous testosterone will recapitulate negative effects on the Akt pathway in castrated ..
  44. Takayama H, Misu H, Iwama H, Chikamoto K, Saito Y, Murao K, et al. Metformin suppresses expression of the selenoprotein P gene via an AMP-activated kinase (AMPK)/FoxO3a pathway in H4IIEC3 hepatocytes. J Biol Chem. 2014;289:335-45 pubmed publisher
    ..that metformin suppresses SEPP1 expression by activating AMP-activated kinase (AMPK) and subsequently inactivating FoxO3a in H4IIEC3 hepatocytes...
  45. Sanphui P, Biswas S. FoxO3a is activated and executes neuron death via Bim in response to ?-amyloid. Cell Death Dis. 2013;4:e625 pubmed publisher
    ..The Forkhead transcription factor FoxO3a has emerged as an important mediator of cell fate including apoptosis...
  46. Davila D, Torres Aleman I. Neuronal death by oxidative stress involves activation of FOXO3 through a two-arm pathway that activates stress kinases and attenuates insulin-like growth factor I signaling. Mol Biol Cell. 2008;19:2014-25 pubmed publisher
    Oxidative stress kills neurons by stimulating FOXO3, a transcription factor whose activity is inhibited by insulin-like growth factor I (IGF-I), a wide-spectrum neurotrophic signal...
  47. Allard D, Figg N, Bennett M, Littlewood T. Akt regulates the survival of vascular smooth muscle cells via inhibition of FoxO3a and GSK3. J Biol Chem. 2008;283:19739-47 pubmed publisher
    ..Importantly, downstream targets of Akt were identified that mediate its protective effect as inhibition of FoxO3a or GSK3 by Akt-dependent phosphorylation protected VSMCs in vitro...
  48. Fujino K, Ogura Y, Sato K, Nedachi T. Potential neuroprotective effects of SIRT1 induced by glucose deprivation in PC12 cells. Neurosci Lett. 2013;557 Pt B:148-53 pubmed publisher
    ..Further, we examined levels of forkhead box O3a (FoxO3a), which is also controlled by changes in extracellular glucose concentration...
  49. Karger S, Weidinger C, Krause K, Sheu S, Aigner T, Gimm O, et al. FOXO3a: a novel player in thyroid carcinogenesis?. Endocr Relat Cancer. 2009;16:189-99 pubmed publisher
    The forkhead box transcription factor FOXO3a has recently been identified as central mediator of the cellular response to oxidative stress inducing cell cycle arrest or apoptosis...
  50. Li D, Luo L, Xu M, Wu J, Chen L, Li J, et al. AMPK activates FOXO3a and promotes neuronal apoptosis in the developing rat brain during the early phase after hypoxia-ischemia. Brain Res Bull. 2017;132:1-9 pubmed publisher
    ..Forkhead transcriptional factor (FOXO3a) has been revealed to be a critical effector of AMPK-mediated celluar apoptosis...
  51. Chi Y, Shi C, Zhao Y, Guo C. Forkhead box O (FOXO) 3 modulates hypoxia-induced autophagy through AMPK signalling pathway in cardiomyocytes. Biosci Rep. 2016;36: pubmed publisher
    ..In addition, we investigated the role of AMPK signalling in the FOXO3-mediated, hypoxia-induced autophagy in H9C2 cells...
  52. Qi X, Chen Z, Xia J, Zheng L, Zhao H, Pi L, et al. FoxO3a suppresses the senescence of cardiac microvascular endothelial cells by regulating the ROS-mediated cell cycle. J Mol Cell Cardiol. 2015;81:114-26 pubmed publisher
    b>FoxO3a plays an important role in the aging process and decreases with age...
  53. Relling D, Esberg L, Fang C, Johnson W, Murphy E, Carlson E, et al. High-fat diet-induced juvenile obesity leads to cardiomyocyte dysfunction and upregulation of Foxo3a transcription factor independent of lipotoxicity and apoptosis. J Hypertens. 2006;24:549-61 pubmed
    ..High-fat diet upregulated the forkhead transcription factor Foxo3a, and suppressed mitochondrial aconitase activity without affecting expression of the caloric sensitive gene silent ..
  54. Han J, Zhao J, Jiang J, Ma X, Liu X, Wang C, et al. Zinc deficiency impairs the renewal of hippocampal neural stem cells in adult rats: involvement of FoxO3a activation and downstream p27(kip1) expression. J Neurochem. 2015;134:879-91 pubmed publisher
    ..rat model, and, using western blot and immunohistochemical analyses, found that the expression of FoxO3a and p27(kip1) was remarkably up-regulated in the rat brain hippocampus...
  55. Wang F, Nguyen M, Qin F, Tong Q. SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction. Aging Cell. 2007;6:505-14 pubmed
    ..We have demonstrated that SIRT2 binds to FOXO3a and reduces its acetylation level...
  56. Ma L, Shen C, Chai J, Yin H, Deng H, Feng R. Extracellular signal-regulated kinase-mammalian target of rapamycin signaling and forkhead-box transcription factor 3a phosphorylation are involved in testosterone's effect on severe burn injury in a rat model. Shock. 2015;43:85-91 pubmed publisher
    ..Administration of testosterone negatively regulated atrogin 1 (Fbxo32) by increasing total and phosphorylated Foxo3a (forkhead-box transcription factor 3a) levels and positively regulated the expression of the mammalian target of ..
  57. Senf S, Dodd S, McClung J, Judge A. Hsp70 overexpression inhibits NF-kappaB and Foxo3a transcriptional activities and prevents skeletal muscle atrophy. FASEB J. 2008;22:3836-45 pubmed publisher
    ..Importantly, the transcriptional activities of Foxo3a and NF-kappaB, which are implicated in the regulation of atrogin-1 and MuRF1, were abolished by Hsp70...
  58. Lee K, Ochi E, Song H, Nakazato K. Activation of AMP-activated protein kinase induce expression of FoxO1, FoxO3a, and myostatin after exercise-induced muscle damage. Biochem Biophys Res Commun. 2015;466:289-94 pubmed publisher
    ..We previously found that levels of Forkhead box proteins, FoxO1 and FoxO3a, and myostatin in rat gastrocnemius increased after exercise-induced muscle damage (EIMD)...
  59. Zheng B, Ohkawa S, Li H, Roberts Wilson T, Price S. FOXO3a mediates signaling crosstalk that coordinates ubiquitin and atrogin-1/MAFbx expression during glucocorticoid-induced skeletal muscle atrophy. FASEB J. 2010;24:2660-9 pubmed publisher
    ..We tested a signaling model in which FOXO3a mediates crosstalk between the PI3K/Akt and MEK/ERK pathways to coordinate AT-1 and UbC expression...
  60. Nadal A, Marrero P, Haro D. Down-regulation of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene by insulin: the role of the forkhead transcription factor FKHRL1. Biochem J. 2002;366:289-97 pubmed
    ..We decided to investigate the molecular mechanism of this inhibition. In the present study, we show that FKHRL1, a member of the forkhead in rhabdosarcoma (FKHR) subclass of the Fox family of transcription factors, stimulates ..
  61. Li Y, Guo Y, Xi M, Yang P, Zhou X, Yin S, et al. Saponins from Aralia taibaiensis attenuate D-galactose-induced aging in rats by activating FOXO3a and Nrf2 pathways. Oxid Med Cell Longev. 2014;2014:320513 pubmed publisher
    ..Further results showed that Forkhead box O3a (FOXO3a), nuclear factor-erythroid 2-related factor 2 (Nrf2), and their targeted antioxidants such as ..
  62. Kang S, Lee H, Kim M, Lee E, Sohn U, Kim I. Forkhead box O3 plays a role in skeletal muscle atrophy through expression of E3 ubiquitin ligases MuRF-1 and atrogin-1 in Cushing's syndrome. Am J Physiol Endocrinol Metab. 2017;312:E495-E507 pubmed publisher
    ..We hypothesized that FOXO3a plays a role in muscle atrophy through expression of the E3 ubiquitin ligases, muscle RING finger protein-1 (MuRF-..
  63. Wang C, Wen J, Zhou Y, Li L, Cui X, Wang J, et al. Apelin induces vascular smooth muscle cells migration via a PI3K/Akt/FoxO3a/MMP-2 pathway. Int J Biochem Cell Biol. 2015;69:173-82 pubmed publisher
    ..Apelin dose-dependently induced phosphorylation of Forkhead box O3a (FoxO3a) and promoted its translocation from the nucleus to cytoplasm, which were blocked by LY294002 and ..
  64. Furukawa Hibi Y, Yoshida Araki K, Ohta T, Ikeda K, Motoyama N. FOXO forkhead transcription factors induce G(2)-M checkpoint in response to oxidative stress. J Biol Chem. 2002;277:26729-32 pubmed
    Members of the FOXO family of mammalian forkhead transcription factors, including AFX, FKHRL1, and FKHR, are homologs of DAF-16, which regulates genes that contribute both to longevity and to resistance to various stresses (including ..
  65. Wang Y, Mu Y, Zhou X, Ji H, Gao X, Cai W, et al. SIRT2-mediated FOXO3a deacetylation drives its nuclear translocation triggering FasL-induced cell apoptosis during renal ischemia reperfusion. Apoptosis. 2017;22:519-530 pubmed publisher
    ..that when SIRT2 was activated by renal ischemia/reperfusion, activated SIRT2 could bind to and deacetylate FOXO3a, promoting FOXO3a nuclear translocation which resulted in an increase of nuclear FOXO3a along with FasL expression ..
  66. Biggs W, Cavenee W, Arden K. Identification and characterization of members of the FKHR (FOX O) subclass of winged-helix transcription factors in the mouse. Mamm Genome. 2001;12:416-25 pubmed
    ..during mammalian development, we have identified and characterized three novel mouse genes; Fkhr1 (Foxo1), Fkhr2 (Foxo3), and Afxh (Foxo4), which are closely related to the human FKHR (Foxo1), AF6q21 (FOXO2), and AFX (FOXO4) genes, ..
  67. Sun L, Zhao M, Wang Y, Liu A, Lv M, Li Y, et al. Neuroprotective effects of miR-27a against traumatic brain injury via suppressing FoxO3a-mediated neuronal autophagy. Biochem Biophys Res Commun. 2017;482:1141-1147 pubmed publisher
    ..Real-time PCR was used to detected miR-27a and Forkhead box O3a (FoxO3a) levels in the hippocampus...
  68. Akhter R, Sanphui P, Biswas S. The essential role of p53-up-regulated modulator of apoptosis (Puma) and its regulation by FoxO3a transcription factor in ?-amyloid-induced neuron death. J Biol Chem. 2014;289:10812-22 pubmed publisher
    ..The transcription factor FoxO3a, which is activated when PI3K/Akt signaling is inhibited, directly binds with the Puma gene and induces its ..
  69. Lv P, Huang J, Yang J, Deng Y, Xu J, Zhang X, et al. Autophagy in muscle of glucose-infusion hyperglycemia rats and streptozotocin-induced hyperglycemia rats via selective activation of m-TOR or FoxO3. PLoS ONE. 2014;9:e87254 pubmed publisher skeletal muscle in glucose-infusion hyperglycemia rats was mediated by the m-TOR pathway while m-TOR and FoxO3 both contributed to enhancement of autophagy in gastrocnemius muscle in streptozotocin-induced hyperglycemia rats...
  70. Esteras N, Alquezar C, Bermejo Pareja F, Bialopiotrowicz E, Wojda U, Martin Requero A. Downregulation of extracellular signal-regulated kinase 1/2 activity by calmodulin KII modulates p21Cip1 levels and survival of immortalized lymphocytes from Alzheimer's disease patients. Neurobiol Aging. 2013;34:1090-100 pubmed publisher
    ..Upregulation of p21 transcription in AD cells appears to be the consequence of increased activity of forkhead box O3a (FOXO3a) as the result of diminished ERK1/2-mediated phosphorylation of this transcription factor, which in ..
  71. Richards J, Sharma S, Falender A, Lo Y. Expression of FKHR, FKHRL1, and AFX genes in the rodent ovary: evidence for regulation by IGF-I, estrogen, and the gonadotropins. Mol Endocrinol. 2002;16:580-99 pubmed
    ..and rat models, we show 1) that FKHR [Forkhead homolog of rhabdomysarcoma = Forkhead box binding protein (Foxo1), FKHRL1 (Forkhead-like protein-1 = Foxo3), and AFX (a Forkhead transcription factor = Foxo4); all defined according to the ..
  72. Wang Y, Liu Y, Chen Y, Shi S, Qin J, Xiao F, et al. Peripheral nerve injury induces down-regulation of Foxo3a and p27kip1 in rat dorsal root ganglia. Neurochem Res. 2009;34:891-8 pubmed publisher
    b>FOXO3a, as a forkhead transcription factor, can control cell cycle through transcriptionally down-regulating p27(kip1) level, which is a key regulator of the mammalian cell cycle and a good candidate to regulate multiple aspects of ..
  73. Zheng W, Kar S, Quirion R. Insulin-like growth factor-1-induced phosphorylation of the forkhead family transcription factor FKHRL1 is mediated by Akt kinase in PC12 cells. J Biol Chem. 2000;275:39152-8 pubmed
    The Forkhead family transcription factor FKHRL1, a mammalian homolog of DAF16 in the nematode Caenorhabditis elegans, is an inducer of apoptosis in its unphosphorylated form and was recently reported as a substrate of Akt kinases...
  74. Ni Y, Berenji K, Wang N, Oh M, Sachan N, Dey A, et al. Foxo transcription factors blunt cardiac hypertrophy by inhibiting calcineurin signaling. Circulation. 2006;114:1159-68 pubmed
    ..However, downstream molecular events are not yet well defined. Here, we report that expression of either Foxo1 or Foxo3 in cardiomyocytes attenuates calcineurin phosphatase activity and inhibits agonist-induced hypertrophic growth...
  75. Nemoto S, Fergusson M, Finkel T. Nutrient availability regulates SIRT1 through a forkhead-dependent pathway. Science. 2004;306:2105-8 pubmed
    ..simultaneously augments expression of the SIRT1 deacetylase and activates the Forkhead transcription factor Foxo3a. Knockdown of Foxo3a expression inhibited the starvation-induced increase in SIRT1 expression...
  76. Peng C, Ma J, Gao X, Tian P, Li W, Zhang L. High glucose induced oxidative stress and apoptosis in cardiac microvascular endothelial cells are regulated by FoxO3a. PLoS ONE. 2013;8:e79739 pubmed publisher
    ..Therefore, the present study was designed to elucidate the potential role of FoxO3a on the CMECs injury induced by high glucose...
  77. Sengupta A, Kalinichenko V, Yutzey K. FoxO1 and FoxM1 transcription factors have antagonistic functions in neonatal cardiomyocyte cell-cycle withdrawal and IGF1 gene regulation. Circ Res. 2013;112:267-77 pubmed publisher
    ..factors have been implicated as positive (forkhead box [Fox] transcription factor M1) and negative (FoxO1 and FoxO3) regulators of cardiomyocyte proliferation prenatally, but their regulatory interactions and functions in neonatal ..
  78. Li D, Li X, Wu J, Li J, Zhang L, Xiong T, et al. Involvement of the JNK/FOXO3a/Bim Pathway in Neuronal Apoptosis after Hypoxic-Ischemic Brain Damage in Neonatal Rats. PLoS ONE. 2015;10:e0132998 pubmed publisher
    ..Previous studies have revealed that forkhead transcription factor (FOXO3a) is a critical effector of JNK-mediated tumor suppression...
  79. Datta S, Ranger A, Lin M, Sturgill J, Ma Y, Cowan C, et al. Survival factor-mediated BAD phosphorylation raises the mitochondrial threshold for apoptosis. Dev Cell. 2002;3:631-43 pubmed
    ..These findings establish a function for endogenous BAD phosphorylation, and elucidate a mechanism by which survival kinases block apoptosis in vivo. ..
  80. Li D, Qu Y, Mao M, Zhang X, Li J, Ferriero D, et al. Involvement of the PTEN-AKT-FOXO3a pathway in neuronal apoptosis in developing rat brain after hypoxia-ischemia. J Cereb Blood Flow Metab. 2009;29:1903-13 pubmed publisher
    ..Previous studies have shown that the Forkhead transcriptional factor (FOXO3a) is a critical effector of the PTEN-mediated tumor suppressor...
  81. Heinke J, Wehofsits L, Zhou Q, Zoeller C, Baar K, Helbing T, et al. BMPER is an endothelial cell regulator and controls bone morphogenetic protein-4-dependent angiogenesis. Circ Res. 2008;103:804-12 pubmed publisher
    ..We show that BMPER is a downstream target of FoxO3a and consistently exerts activating effects on endothelial cell sprouting and migration in vitro and in vivo...
  82. Wang S, Chong Z, Shang Y, Maiese K. WISP1 neuroprotection requires FoxO3a post-translational modulation with autoregulatory control of SIRT1. Curr Neurovasc Res. 2013;10:54-69 pubmed
    ..Here we demonstrate that WISP1 prevents forkhead transcription factor FoxO3a mediated caspase 1 and caspase 3 apoptotic cell death in primary neurons during oxidant stress...
  83. Kress T, Cannell I, Brenkman A, Samans B, Gaestel M, Roepman P, et al. The MK5/PRAK kinase and Myc form a negative feedback loop that is disrupted during colorectal tumorigenesis. Mol Cell. 2011;41:445-57 pubmed publisher
    ..MK5 activates miR-34b/c expression via phosphorylation of FoxO3a, thereby promoting nuclear localization of FoxO3a and enabling it to induce miR-34b/c expression and arrest ..
  84. Kumarswamy R, Lyon A, Volkmann I, Mills A, Bretthauer J, Pahuja A, et al. SERCA2a gene therapy restores microRNA-1 expression in heart failure via an Akt/FoxO3A-dependent pathway. Eur Heart J. 2012;33:1067-75 pubmed publisher
    ..SERCA2a gene delivery. Increased Akt activation in cultured cardiomyocytes led to phosphorylation of FoxO3A and subsequent exclusion from the nucleus, resulting in miR-1 gene silencing...