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 SOX9
Homo sapiens
 HIF1A
Homo sapiens
 Pax6
Mus musculus
 PAX6
Homo sapiens
 Snai2
Mus musculus
 PPARA
Homo sapiens
 Ppara
Mus musculus
 Thrb
Mus musculus
 SNAI2
Homo sapiens
 Tbr1
Mus musculus
Transcription Factor Encyclopedia  BETA
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Overview

FOXO3 is known to regulate the expression of a wide range of genes, both positively and negatively. Its activity is broadly anti-proliferative, and many of its targets are linked to apoptosis, including FASLG (FasL), BCL2L11 (Bim), TNFSF10 (TRAIL), and BBC3 (PUMA). In fact, expression of PUMA is thought to be essential for FOXO3a-induced cell death [1].

As well as these, FOXO3 regulates transcription of important cell cycle control and checkpoint proteins such as CDKN1A (p21Cip1), CDKN2D (p19INK4a) and ATM. Although it is considered a tumour suppressor, FOXO3a has been recorded as upregulating ABCB1 (aka MDR1, P-glycoprotein), hindering the treatment of cancer by chemotherapy [2]. FOXO3 is involved in protection from oxidative stress, by upregulating the reactive oxygen species scavengers CAT (catalase) and SOD2 (MnSOD), as well as SESN3 (sestrin 3) and PINK1. FOXO3a also plays a role in metabolism, regulating expression of genes such as G6PC (glucose-6-phosphatase) and IGFBP1.

FOXO3 participates in various feedback loops. For example, it upregulates a subunit of PI3K (PIK3CA), upstream of the inhibitory protein Akt. On the other hand, FOXO3a is also thought to increase expression of DUSP-5 and -6 [3], which act on MAP kinases such as Erk (which usually represses FOXO3 activity).

References
  1. You H et al. Regulation of transactivation-independent proapoptotic activity of p53 by FOXO3a. Proc. Natl. Acad. Sci. U.S.A., 103(24):9051-6. (PMID 16757565)
  2. Hui RC et al. Doxorubicin activates FOXO3a to induce the expression of multidrug resistance gene ABCB1 (MDR1) in K562 leukemic cells. Mol. Cancer Ther., 7(3):670-8. (PMID 18347152)
  1. Delpuech O et al. Induction of Mxi1-SR alpha by FOXO3a contributes to repression of Myc-dependent gene expression. Mol. Cell. Biol., 27(13):4917-30. (PMID 17452451)
Targets (author curated)
  Target gene TF complex Effect References GO terms (biological process)
1 ABCB1 (human) (none provided)
18347152 3 terms found
2 Atm (mouse) (none provided)
18424439 25 terms found
3 Bbc3 (mouse) (none provided)
16801400 9 terms found
4 Bcl2l11 (rat) (none provided)
12913110 29 terms found
5 BCL6 (human) (none provided)
15509806 30 terms found
6 BNIP3L (human) (none provided)
16166289 5 terms found
7 Btg1 (mouse) (none provided)
14734530 5 terms found
8 CAT (human) (none provided)
11884717 14 terms found
9 Ccng2 (rat) (none provided)
14966295 2 terms found
10 CDKN1A (human) (none provided)
15084259 30 terms found
11 Cdkn1b (rat) (none provided)
11094066 29 terms found
12 CDKN2B (human) (none provided)
17873901 15 terms found
13 CDKN2D (human) (none provided)
17873901 14 terms found
14 Cited2 (rat) (none provided)
17353275 57 terms found
embryonic process involved in female pregnancy   embryonic process involved in female pregnancy   decidualization   decidualization   positive regulation of transcription   positive regulation of transcription, DNA-dependent   positive regulation of transcription   positive regulation of transcription, DNA-dependent   positive regulation of cell cycle   positive regulation of cell cycle   response to fluid shear stress   positive regulation of transforming growth factor beta receptor signaling pathway   response to fluid shear stress   negative regulation of cell migration   positive regulation of transforming growth factor beta receptor signaling pathway   negative regulation of cell migration   adrenal gland development   adrenal gland development   positive regulation of cell-cell adhesion   positive regulation of cell-cell adhesion   negative regulation of transcription   negative regulation of gene expression   positive regulation of gene expression   negative regulation of gene expression   positive regulation of gene-specific transcription from RNA polymerase II promoter   positive regulation of gene expression   positive regulation of gene-specific transcription from RNA polymerase II promoter   cell proliferation   cell proliferation   heart development   heart development   central nervous system development   central nervous system development   determination of left/right symmetry   determination of left/right symmetry   anti-apoptosis   negative regulation of transcription, mitotic   regulation of transcription from RNA polymerase II promoter   anti-apoptosis   morphogenesis of an epithelium   embryonic placenta development   embryonic placenta development   liver development   liver development   trophectodermal cell differentiation   trophectodermal cell differentiation   kidney development   response to hypoxia   in utero embryonic development   response to hypoxia   branching involved in ureteric bud morphogenesis   vasculogenesis   vasculogenesis   blood vessel development   blood vessel development   negative regulation of transcription from RNA polymerase II promoter   negative regulation of transcription from RNA polymerase II promoter  
15 DUSP5 (human) (none provided)
17452451 1 terms found
16 DUSP6 (human) (none provided)
17452451 9 terms found
17 ESR1 (human) (none provided)
15367686 22 terms found
18 FASLG (human) (none provided)
10102273 25 terms found
19 Fbxo32 (mouse) (none provided)
15109499 2 terms found
20 G6PC (human) (none provided)
16840535 12 terms found
21 Gadd45a (rat) (none provided)
11964479 9 terms found
22 ID1 (human) (none provided)
17132628 20 terms found
23 Igfbp1 (rat) (none provided)
10913147 5 terms found
24 KLF4 (human) (none provided)
18375530 5 terms found
25 NOS3 (human) (none provided)
16100571 43 terms found
oxidation reduction   response to hyperoxia   response to lipoprotein stimulus   negative regulation of calcium ion transport   negative regulation of hydrolase activity   regulation of blood vessel size (NAS, 7504210)   regulation of blood vessel size   negative regulation of smooth muscle cell proliferation   positive regulation of vasodilation (NAS, 18048451)   positive regulation of angiogenesis   response to ethanol   endothelial cell migration (IMP, 8999856)   response to peptide hormone stimulus   negative regulation of potassium ion transport   response to amino acid stimulus   response to drug   response to fluid shear stress (IEP, 10376603)   response to cytokine stimulus   response to lipopolysaccharide   response to estradiol stimulus   lipopolysaccharide-mediated signaling pathway   positive regulation of guanylate cyclase activity   positive regulation of guanylate cyclase activity (IMP, 17502619)   lung development   smooth muscle hyperplasia   negative regulation of muscle hyperplasia   response to organic cyclic substance   negative regulation of platelet activation (NAS, 7504210)   response to lead ion   response to heat (NAS, 18048451)   negative regulation of cell proliferation   regulation of blood pressure (NAS, 7504210)   aging   signal transduction   mitochondrion organization   anti-apoptosis   nitric oxide biosynthetic process (IDA, 7488039)   arginine catabolic process (IDA, 1378832)   regulation of systemic arterial blood pressure by endothelin (IMP, 8999856)   regulation of sodium ion transport   blood vessel remodeling   response to hypoxia   ovulation from ovarian follicle  
26 PIK3CA (human) (none provided)
18644865 8 terms found
27 PINK1 (human) (none provided)
19276113 11 terms found
28 Plk1 (mouse) (none provided)
11607034 6 terms found
29 PRDX3 (human) (none provided)
18195003 17 terms found
30 RBL2 (human) (none provided)
11884591 4 terms found
31 Sesn3 (mouse) (none provided)
19061837 2 terms found
32 SOD2 (human) (none provided)
12239572 45 terms found
oxidation reduction   response to hyperoxia   iron ion homeostasis   protein homotetramerization (IPI, 19265433)   regulation of mitochondrial membrane potential   hydrogen peroxide biosynthetic process   regulation of catalytic activity   erythrophore differentiation   response to axon injury   negative regulation of fibroblast proliferation   neuron development   negative regulation of fat cell differentiation   positive regulation of nitric oxide biosynthetic process   superoxide anion generation   negative regulation of apoptosis (IMP, 12551919)   negative regulation of neuron apoptosis (IGI, 17251466)   response to drug   oxygen homeostasis (IMP, 16179351)   response to hydrogen peroxide   response to nutrient levels   respiratory electron transport chain   hemopoiesis   removal of superoxide radicals (IMP, 16179351)   response to activity   post-embryonic development   response to gamma radiation   negative regulation of cell proliferation (IMP, 16179351)   locomotory behavior   regulation of blood pressure   heart development   aging   mitochondrion organization   superoxide metabolic process (IMP, 12551919)   anti-apoptosis   superoxide metabolic process (IDA, 14980699)   glutathione metabolic process   regulation of transcription from RNA polymerase II promoter (IMP, 9393747)   vasodilation by acetylcholine involved in regulation of systemic arterial blood pressure   detection of oxygen   release of cytochrome c from mitochondria   liver development   response to hypoxia   age-dependent response to reactive oxygen species (IMP, 14980699)   response to superoxide (IMP, 16179351)   age-dependent response to oxidative stress  
33 TNFSF10 (human) (none provided)
12351634 6 terms found
34 Trim63 (rat) (none provided)
15781459 2 terms found
Targets (automatically populated)
About this section
Data found in this section is cached from PAZAR, a public database of transcription factor and regulatory sequence annotation. Visit PAZAR at http://www.pazar.info/.
  Target gene TF complex Effect References GO terms (biological process)
1 BCL2L11 (human) pazar FOXO3_HUMAN
15688014 23 terms found
2 ESR1 (human) pazar FOXO3_HUMAN
16807346 22 terms found
3 G6pc (mouse) pazar FOXO3_HUMAN
16840535 19 terms found
4 ID1 (human) pazar FOXO3_HUMAN
17132628 20 terms found
5 SOD2 (human) pazar FOXO3_HUMAN
12239572 45 terms found
oxidation reduction   response to hyperoxia   iron ion homeostasis   protein homotetramerization (IPI, 19265433)   regulation of mitochondrial membrane potential   hydrogen peroxide biosynthetic process   regulation of catalytic activity   erythrophore differentiation   response to axon injury   negative regulation of fibroblast proliferation   neuron development   negative regulation of fat cell differentiation   positive regulation of nitric oxide biosynthetic process   superoxide anion generation   negative regulation of apoptosis (IMP, 12551919)   negative regulation of neuron apoptosis (IGI, 17251466)   response to drug   oxygen homeostasis (IMP, 16179351)   response to hydrogen peroxide   response to nutrient levels   respiratory electron transport chain   hemopoiesis   removal of superoxide radicals (IMP, 16179351)   response to activity   post-embryonic development   response to gamma radiation   negative regulation of cell proliferation (IMP, 16179351)   locomotory behavior   regulation of blood pressure   heart development   aging   mitochondrion organization   superoxide metabolic process (IMP, 12551919)   anti-apoptosis   superoxide metabolic process (IDA, 14980699)   glutathione metabolic process   regulation of transcription from RNA polymerase II promoter (IMP, 9393747)   vasodilation by acetylcholine involved in regulation of systemic arterial blood pressure   detection of oxygen   release of cytochrome c from mitochondria   liver development   response to hypoxia   age-dependent response to reactive oxygen species (IMP, 14980699)   response to superoxide (IMP, 16179351)   age-dependent response to oxidative stress  
6 TNFSF10 (human) pazar FOXO3_HUMAN
(unknown)
12351634 6 terms found