forkhead box protein o3


Summary: A forkhead box transcription factor and transcriptional activator which triggers type 1 programmed cell death (APOPTOSIS) in the absence of APOPTOSIS INHIBITING PROTEINS, including neuronal cell death induced by OXIDATIVE STRESS. It recognizes and binds to the DNA sequence 5'-(AG)TAAA(TC)A-3' and also functions in post-transcriptional regulation of the c-MYC PROTO-ONCOGENE.

Top Publications

  1. Eisenstein M. Centenarians: Great expectations. Nature. 2012;492:S6-8 pubmed publisher
  2. Zaal A, Nota B, Moore K, Dieker M, Van Ham S, ten Brinke A. TLR4 and C5aR crosstalk in dendritic cells induces a core regulatory network of RSK2, PI3K?, SGK1, and FOXO transcription factors. J Leukoc Biol. 2017;102:1035-1054 pubmed publisher
    ..Our findings shed new light on the depth and complexity of C5aR and TLR4 crosstalk and provide new foci of research for future studies. ..
  3. Lo C, Shi Y, Chenier I, Ghosh A, Wu C, Cailhier J, et al. Heterogeneous Nuclear Ribonucleoprotein F Stimulates Sirtuin-1 Gene Expression and Attenuates Nephropathy Progression in Diabetic Mice. Diabetes. 2017;66:1964-1978 pubmed publisher
    ..Our results demonstrate that hnRNP F protects kidneys against oxidative stress and nephropathy via stimulation of Sirtuin-1 expression and signaling in diabetes. ..
  4. Nagarajan A, Dogra S, Sun L, Gandotra N, Ho T, Cai G, et al. Paraoxonase 2 Facilitates Pancreatic Cancer Growth and Metastasis by Stimulating GLUT1-Mediated Glucose Transport. Mol Cell. 2017;67:685-701.e6 pubmed publisher
    ..Collectively, our results identify PON2 as a new modulator of glucose transport that regulates a pharmacologically tractable pathway necessary for PDAC tumor growth and metastasis. ..
  5. Nie Y, Sun L, Wu Y, Yang Y, Wang J, He H, et al. AKT2 Regulates Pulmonary Inflammation and Fibrosis via Modulating Macrophage Activation. J Immunol. 2017;198:4470-4480 pubmed publisher
    ..Collectively, these results indicate that AKT2 modulates pulmonary fibrosis through inducing TGF-?1 and IL-13 production by macrophages, and inhibition of AKT2 may be a potential strategy for treating IPF. ..
  6. Sereni M, Baldelli E, Gambara G, Ravaggi A, Hodge K, Alberts D, et al. Kinase-driven metabolic signalling as a predictor of response to carboplatin-paclitaxel adjuvant treatment in advanced ovarian cancers. Br J Cancer. 2017;117:494-502 pubmed publisher
    ..If validated in a larger cohort of patients, the decreased AMPK-AKT-mTOR activation and phosphorylation of FOXO1 T24/FOXO3 T32 may help identify carboplatin-paclitaxel-resistant EOC patients. ..
  7. Cheng Q, Wu L, Tu R, Wu J, Kang W, Su T, et al. Mycoplasma fermentans deacetylase promotes mammalian cell stress tolerance. Microbiol Res. 2017;201:1-11 pubmed publisher
    ..Mycoplasmal deacetylase also alters the performance of cells under drug stress. This study expands our understanding of the potential molecular and cellular mechanisms of interaction between mycoplasmas and mammalian cells. ..
  8. Kumazoe M, Takai M, Hiroi S, Takeuchi C, Kadomatsu M, Nojiri T, et al. The FOXO3/PGC-1? signaling axis is essential for cancer stem cell properties of pancreatic ductal adenocarcinoma. J Biol Chem. 2017;292:10813-10823 pubmed publisher
    ..This suggests that cGMP induction and PGC-1? inhibition represent potential strategies for treating patients with pancreatic ductal adenocarcinoma. ..
  9. Luo X, Yang Z, Liu X, Liu Z, Miao X, Li D, et al. The clinicopathological significance of forkhead box P1 and forkhead box O3a in pancreatic ductal adenocarcinomas. Tumour Biol. 2017;39:1010428317699129 pubmed publisher
    ..6568-0.742). Loss of forkhead box P1 and forkhead box O3a protein expression is associated with carcinogenesis, progression, and poor prognosis in patients with pancreatic ductal adenocarcinomas. ..

More Information


  1. Singh V, Prakhar P, Rajmani R, Mahadik K, Borbora S, Balaji K. Histone Methyltransferase SET8 Epigenetically Reprograms Host Immune Responses to Assist Mycobacterial Survival. J Infect Dis. 2017;216:477-488 pubmed publisher
  2. Qian Z, Ren L, Wu D, Yang X, Zhou Z, Nie Q, et al. Overexpression of FoxO3a is associated with glioblastoma progression and predicts poor patient prognosis. Int J Cancer. 2017;140:2792-2804 pubmed publisher
    ..FoxO3a might be a novel prognostic biomarker or a potential therapeutic target in glioblastoma. ..
  3. Yu W, Ni Y, Saji M, Ringel M, Jaini R, Eng C. Cowden syndrome-associated germline succinate dehydrogenase complex subunit D (SDHD) variants cause PTEN-mediated down-regulation of autophagy in thyroid cancer cells. Hum Mol Genet. 2017;26:1365-1375 pubmed publisher
    ..Overall, our study reveals a novel mechanism of crosstalk amongst SDHD, PTEN and autophagy pathways and their potential roles in thyroid carcinogenesis. ..
  4. Cheng M, An S, Li J. Identifying key genes associated with acute myocardial infarction. Medicine (Baltimore). 2017;96:e7741 pubmed publisher
  5. Li L, Lyu D. [Preparation and characterization of mouse polyclonal antibody against conserved region of human FOXO3]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2017;33:838-844 pubmed
    ..Conclusion The polyclonal antibody against conserved domain of FOXO3 can identify the endogenous FOXO3 protein. It can be used to analyze the endogenous FOXO3 expression level. ..
  6. Park J, Lee Y, Bae Y. Protein kinase C downregulation induces senescence via FoxO3a inhibition in HCT116 and HEK293 cells. Biochem Biophys Res Commun. 2017;493:1548-1554 pubmed publisher
    ..Therefore, this study suggests for the first time that downregulation of PKC induces senescence through the AKT-FoxO3a-ROS-p53-p21Cip1/WAF1 pathway in HCT116 and HEK293 cells...
  7. Liu W, Wang X, Liu Z, Wang Y, Yin B, Yu P, et al. SGK1 inhibition induces autophagy-dependent apoptosis via the mTOR-Foxo3a pathway. Br J Cancer. 2017;117:1139-1153 pubmed publisher
    ..Although inhibition of SGK1 has been shown to delay cancer progression, the underlying mechanisms have not yet been elucidated...
  8. Li L, Zviti R, Ha C, Wang Z, Hill J, Lin F. Forkhead box O3 (FoxO3) regulates kidney tubular autophagy following urinary tract obstruction. J Biol Chem. 2017;292:13774-13783 pubmed publisher
    ..Taken together, our findings indicate that FoxO3 activation can both induce and maintain autophagic activities in renal epithelial cells in response to injury from urinary tract obstruction. ..
  9. Fitzwalter B, Towers C, Sullivan K, Andrysik Z, Hoh M, Ludwig M, et al. Autophagy Inhibition Mediates Apoptosis Sensitization in Cancer Therapy by Relieving FOXO3a Turnover. Dev Cell. 2018;44:555-565.e3 pubmed publisher
    ..Thus, a link between two processes mediated via a single transcription factor binding site in the genome can be leveraged to improve anti-cancer therapies. ..
  10. Chuang P, Cai W, Li X, Fang L, Xu J, Yacoub R, et al. Reduction in podocyte SIRT1 accelerates kidney injury in aging mice. Am J Physiol Renal Physiol. 2017;313:F621-F628 pubmed publisher
    ..Together, our data suggest that SIRT1 may be a potential therapeutic target to treat patients with aging-related kidney disease. ..
  11. Peng X, So K, He L, Zhao Y, Zhou J, Li Y, et al. MyoD- and FoxO3-mediated hotspot interaction orchestrates super-enhancer activity during myogenic differentiation. Nucleic Acids Res. 2017;45:8785-8805 pubmed publisher
    ..Finally, we show MyoD and FoxO3 are key in orchestrating the Myogenin hotspots interaction and activation. Altogether our results identify muscle-specific SEs and provide mechanistic insights into the functionality of SE. ..
  12. Xu K, Zhang Z, Pei H, Wang H, Li L, Xia Q. FoxO3a induces temozolomide resistance in glioblastoma cells via the regulation of ?-catenin nuclear accumulation. Oncol Rep. 2017;37:2391-2397 pubmed publisher
    ..Taken together, these findings strongly support that FoxO3a renders GBM cells resistant to TMZ treatment, at least in part, through the regulation of ?-catenin nuclear accumulation. ..
  13. Gruel N, Benhamo V, Bhalshankar J, Popova T, Freneaux P, Arnould L, et al. Polarity gene alterations in pure invasive micropapillary carcinomas of the breast. Breast Cancer Res. 2014;16:R46 pubmed publisher
  14. Zhang H, Zhao Z, Pang X, Yang J, Yu H, Zhang Y, et al. MiR-34a/sirtuin-1/foxo3a is involved in genistein protecting against ox-LDL-induced oxidative damage in HUVECs. Toxicol Lett. 2017;277:115-122 pubmed publisher
    ..The present study suggests that miR-34a/sirtuin-1/foxo3a might play an important role in genistein reversing ox-LDL-induced oxidative damage in HUVECs. ..
  15. Liu Y, Lv J, Zeng Q, Shen S, Xing J, Zhang Y, et al. AMPK activation ameliorates D-GalN/LPS-induced acute liver failure by upregulating Foxo3A to induce autophagy. Exp Cell Res. 2017;358:335-342 pubmed publisher
    ..In addition, AMPK activation alleviated liver failure in vitro. Thus, AMPK/Foxo3A/autophagy pathway may be an effective treatment approach to ameliorate ALF. ..
  16. Bulstrode H, Johnstone E, Marqués Torrejón M, Ferguson K, Bressan R, Blin C, et al. Elevated FOXG1 and SOX2 in glioblastoma enforces neural stem cell identity through transcriptional control of cell cycle and epigenetic regulators. Genes Dev. 2017;31:757-773 pubmed publisher
    ..Thus, FOXG1 and SOX2 operate in complementary but distinct roles to fuel unconstrained self-renewal in GBM stem cells via transcriptional control of core cell cycle and epigenetic regulators. ..
  17. Andrade G, da Silveira J, Perrini C, Del Collado M, Gebremedhn S, Tesfaye D, et al. The role of the PI3K-Akt signaling pathway in the developmental competence of bovine oocytes. PLoS ONE. 2017;12:e0185045 pubmed publisher
  18. Zhang L, Cai M, Gong Z, Zhang B, Li Y, Guan L, et al. Geminin facilitates FoxO3 deacetylation to promote breast cancer cell metastasis. J Clin Invest. 2017;127:2159-2175 pubmed publisher
    ..These results underscore a prominent role for geminin in promoting breast cancer metastasis via the enzyme-substrate-coupling mechanism in HDAC3-FoxO3 complex formation. ..
  19. Choi R, McConahay A, Jeong H, McClellan J, Hardee J, Carson J, et al. Tribbles 3 regulates protein turnover in mouse skeletal muscle. Biochem Biophys Res Commun. 2017;493:1236-1242 pubmed publisher
    ..These findings indicate that TRB3 regulates protein synthesis and breakdown via the Akt/mTOR/FoxO pathways. ..
  20. Kenny T, Hart P, Ragazzi M, Sersinghe M, Chipuk J, Sagar M, et al. Selected mitochondrial DNA landscapes activate the SIRT3 axis of the UPRmt to promote metastasis. Oncogene. 2017;36:4393-4404 pubmed publisher
    ..We propose that the ability of selected mtDNA species to activate the UPRmt is a process that is exploited by cancer cells to maintain mitochondrial fitness and facilitate metastasis. ..
  21. Cheong J, Zhang F, Chua P, Bay B, Thorburn A, Virshup D. Casein kinase 1α-dependent feedback loop controls autophagy in RAS-driven cancers. J Clin Invest. 2015;125:1401-18 pubmed publisher
    ..Together, our results identify a kinase feedback loop that influences RAS-dependent autophagy and suggest that targeting CK1α-regulated autophagy offers a potential therapeutic opportunity to treat oncogenic RAS-driven cancers. ..