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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

As well as with the many proteins that covalently modify it, FOXO3a performs protein-protein interactions with a range of other binding partners. Some of the most important of these are the 14-3-3 proteins, which bind phosphorylated FOXO3a (in the nucleus or cytoplasm) and inactivate it, particularly by sequestration in the cytoplasm [1].

In cell cycle and apoptosis regulation, FOXO3a directly binds p53's DBD (promoting its translocation into the cytoplasm) with its transactivation and forkhead domains. These FOXO3 domains also interact intramolecularly with each other [2]. FOXO3a also binds to the checkpoint and repair protein ATM, possibly increasing its activity [3]. The transcription factor and tumour suppressor RUNX3, often lost in gastric cancer, physically interacts with FOXO3 to enhance Bim expression and induce apoptosis [4].

FOXO3a is known to interact with both ER (estrogen receptor) α and ERβ, albeit via different domains, resulting in a reduction in ER-mediated transcription [5]. It is likely that FOXO3a similarly binds to other nuclear receptors PR (progesterone receptor) and AR (androgen receptor), as this has been recorded for FOXO1 [6][7]. In the Wnt pathway, FOXO3a competes with the T cell factor class of transcription factors for β-catenin binding. FOXO3-β-catenin binding increases with oxidative stress [8][9].

References
  1. Brunet A et al. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell, 96(6):857-68. (PMID 10102273)
  2. Wang F et al. Biochemical and structural characterization of an intramolecular interaction in FOXO3a and its binding with p53. J. Mol. Biol., 384(3):590-603. (PMID 18824006)
  3. Tsai WB et al. Functional interaction between FOXO3a and ATM regulates DNA damage response. Nat. Cell Biol., 10(4):460-7. (PMID 18344987)
  4. Yamamura Y et al. RUNX3 cooperates with FoxO3a to induce apoptosis in gastric cancer cells. J. Biol. Chem., 281(8):5267-76. (PMID 16373335)
  5. Zou Y et al. Forkhead box transcription factor FOXO3a suppresses estrogen-dependent breast cancer cell proliferation and tumorigenesis. Breast Cancer Res., 10(1):R21. (PMID 18312651)
  1. Ward EC et al. The regulation and function of the forkhead transcription factor, Forkhead box O1, is dependent on the progesterone receptor in endometrial carcinoma. Endocrinology, 149(4):1942-50. (PMID 18096667)
  2. Ma Q et al. FoxO1 mediates PTEN suppression of androgen receptor N- and C-terminal interactions and coactivator recruitment. Mol. Endocrinol., 23(2):213-25. (PMID 19074551)
  3. Almeida M et al. Oxidative stress antagonizes Wnt signaling in osteoblast precursors by diverting beta-catenin from T cell factor- to forkhead box O-mediated transcription. J. Biol. Chem., 282(37):27298-305. (PMID 17623658)
  4. Hoogeboom D et al. Interaction of FOXO with beta-catenin inhibits beta-catenin/T cell factor activity. J. Biol. Chem., 283(14):9224-30. (PMID 18250171)
Ligands (author curated)
There are no data here... Yet.
Interactions (author curated)
  Interactor Experiment Types and Papers Nature of Interaction
1 AKT1 (human)
Biochemical Activity
10102273
Physical: enzyme modification: phosphorylation
2 ATM (human)
Affinity Capture-Western
18344987
Not specified
3 CTNNB1 (human)
Affinity Capture-Western
15905404
Not specified
4 EP300 (human)
Affinity Capture-Western
11896584
Physical: enzyme modification: acetylation
5 ESR1 (human)
Affinity Capture-Western
18312651
Not specified
6 ESR2 (human)
Affinity Capture-Western
18312651
Not specified
7 FOXG1 (human)
Affinity Capture-Western
15084259
Not specified
8 FOXM1 (human)
Affinity Capture-Western
16809346
Not specified
9 HIF1A (human)
Affinity Capture-Western
18268343
Not specified
10 IKBKB (human)
Affinity Capture-Western
15084260
Physical: enzyme modification: phosphorylation
11 KAT2B (human)
Affinity Capture-Western
14976264
Not specified
12 MAPK1 (human)
Affinity Capture-Western
10102273
Physical: enzyme modification: phosphorylation
13 MDM2 (human)
Affinity Capture-Western
10102273
Physical: ubiquitination
14 PPP2CA (human)
Not specified
17322870, 19029949
Physical: dephosphorylation
15 PRMT1 (human)
Invitro
18951090
Physical: enzyme modification: methylation
16 RUNX3 (human)
Affinity Capture-Western
16373335
Not specified
17 SGK1 (human)
Biochemical Activity
11154281
Physical: enzyme modification: phosphorylation
18 SIRT1 (human)
Affinity Capture-Western
14980222, 15917664
Physical: deacetylation
19 SIRT2 (human)
Affinity Capture-Western
17521387
Physical: deacetylation
20 STK4 (human)
Affinity Capture-Western
16751106
Physical: enzyme modification: phosphorylation
21 TP53 (human)
Affinity Capture-Western
16757565
Not specified
22 YWHAB (human)
Affinity Capture-Western
16751106
Physical: sequestering
Interactions (automatically populated)
  Interactor Experiment Types and Papers Nature of Interaction
1 SMAD3 Affinity Capture-Western
15084259
Not specified
2 SMAD4 Affinity Capture-Western
15084259
Not specified
3 USP7 Affinity Capture-Western
16964248
(not specified by author)
4 YWHAZ Affinity Capture-Western
10102273
Physical: sequestering
Transcriptional regulators (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/.
  Regulating TF complex Regulating TF Genomic links GO terms (biological process) Pubmed
1
HIFALPHA
TF0001144
ARNT
Homo sapiens
ENSG00000143437
405 (Entrez Gene)
(no terms found) 20061373
2
HIFALPHA
TF0001144
HIF1A
Homo sapiens
ENSG00000100644
3091 (Entrez Gene)
(no terms found) 20061373
3
HIFALPHA
TF0001144
EPAS1
Homo sapiens
ENSG00000116016
2034 (Entrez Gene)
(no terms found) 20061373
4
HIFALPHA
TF0001144
ARNT
Homo sapiens
ENSG00000143437
405 (Entrez Gene)
(no terms found) 20061373
5
HIFALPHA
TF0001144
HIF1A
Homo sapiens
ENSG00000100644
3091 (Entrez Gene)
(no terms found) 20061373
6
HIFALPHA
TF0001144
EPAS1
Homo sapiens
ENSG00000116016
2034 (Entrez Gene)
(no terms found) 20061373
7
HIFALPHA
TF0001144
ARNT
Homo sapiens
ENSG00000143437
405 (Entrez Gene)
(no terms found) 20061373
8
HIFALPHA
TF0001144
HIF1A
Homo sapiens
ENSG00000100644
3091 (Entrez Gene)
(no terms found) 20061373
9
HIFALPHA
TF0001144
EPAS1
Homo sapiens
ENSG00000116016
2034 (Entrez Gene)
(no terms found) 20061373
10
HIFALPHA
TF0001144
ARNT
Homo sapiens
ENSG00000143437
405 (Entrez Gene)
(no terms found) 20061373
11
HIFALPHA
TF0001144
HIF1A
Homo sapiens
ENSG00000100644
3091 (Entrez Gene)
(no terms found) 20061373
12
HIFALPHA
TF0001144
EPAS1
Homo sapiens
ENSG00000116016
2034 (Entrez Gene)
(no terms found) 20061373