Phospho-FOXO1 (S256) Antibody

The Phospho-FOXO1 (S256) antibody targets a transcription factor that plays a central role in insulin signaling and metabolic homeostasis, particularly in response to oxidative stress. This protein binds to the insulin response element (IRE) with a consensus sequence of 5'-TT[G/A]TTTTG-3' and the related Daf-16 family binding element (DBE) with a consensus sequence of 5'-TT[G/A]TTTAC-3'. Its activity is suppressed by insulin. FOXO1 is a key regulator of redox balance and osteoblast numbers, thereby controlling bone mass and orchestrating the endocrine function of the skeleton in glucose metabolism regulation. Furthermore, it acts as a crucial regulator of chondrogenic commitment in skeletal progenitor cells, responding to lipid availability: under low lipid conditions, it translocates to the nucleus, promoting SOX9 expression, which in turn induces chondrogenic commitment and suppresses fatty acid oxidation. FOXO1 synergistically interacts with ATF4 to suppress osteocalcin/BGLAP activity, leading to increased glucose levels and triggering glucose intolerance and insulin resistance. It also suppresses the transcriptional activity of RUNX2, an upstream activator of osteocalcin/BGLAP. In hepatocytes, FOXO1 promotes gluconeogenesis by cooperating with PPARGC1A and CEBPA to activate the expression of genes such as IGFBP1, G6PC1, and PCK1. FOXO1 is a significant regulator of cell death, acting downstream of CDK1, PKB/AKT1, and STK4/MST1, promoting neural cell death. It mediates insulin's effects on adipose tissue, regulating the expression of adipogenic genes such as PPARG during preadipocyte differentiation, and influencing adipocyte size and adipose tissue-specific gene expression in response to excessive calorie intake. It also regulates the transcriptional activity of GADD45A and the repair of nitric oxide-damaged DNA in beta-cells. Importantly, FOXO1 is required for autophagic cell death induction in response to starvation or oxidative stress, independently of its transcriptional activity. Finally, FOXO1 mediates the function of MLIP in cardiomyocyte hypertrophy and cardiac remodeling, and regulates endothelial cell (EC) viability and apoptosis in a PPIA/CYPA-dependent manner via the transcription of CCL2 and BCL2L11, which are involved in EC chemotaxis and apoptosis.

Numerous studies highlight the significant role of FOXO1 in various biological processes and disease states. The following are key findings from recent research:

1. FOXO1 downregulation by miR300 in hepatocellular carcinoma (HCC) cells and its mediation of miR300-induced cell viability. PMID: 30272296
2. Loss of FOXO1 protein as an early event in pancreatic ductal adenocarcinoma development, potentially independent of the top four mutated cancer genes. PMID: 30227407
3. The impact of FOXO1/3 activity on cardiac regeneration, with FOXO1 largely exhibiting detrimental effects in the heart, while FOXO3's actions are cell-type dependent. [review] PMID: 27890702
4. MALAT1's repression of sirtuin 1 (SIRT1) expression through targeting FOXO1. PMID: 29928873
5. FOXO1 upregulation in cardiomyocytes as central to the pathogenesis of CIH-induced cardiac hypertrophy. PMID: 28738025
6. Elatoside C's attenuation of ox-LDL-induced HUVECs injury by inducing autophagy via increased FOXO1 expression, suggesting its potential as a therapeutic agent for atherosclerosis. PMID: 28189723
7. MiR-145's suppression of human adipose-derived mesenchymal stem cells' osteoinductive differentiation through direct FOXO1 suppression. PMID: 29249185
8. The interaction between MEK and AKT affecting cell migration and adhesion, involving phosphorylation of the migration-related transcription factor FOXO1. PMID: 28225038
9. Isorhapontigenin's upregulation of p27 expression via enhanced FOXO1 binding to its promoter and decreased miR-182 binding to its mRNA 3'-UTR. PMID: 29409027
10. miR660's oncogenic role in osteosarcoma (OS) by directly targeting FOXO1, suggesting its potential as a therapeutic target. PMID: 29901128
11. The molecular mechanisms determining the switch between pro-apoptotic and pro-survival effects of FOXO1 and their interplay with differentiation programs. PMID: 28774833
12. Potential therapeutic targets for indirect interference with PAX3-FOXO1 activity in alveolar rhabdomyosarcoma. PMID: 29146205
13. FOXO1 as a potent therapeutic target in digestive malignancy. PMID: 28965871
14. Association of low FOXO1 expression with ovarian cancer. PMID: 30138596
15. Foxo1's involvement in estradiol 17beta-mediated proliferation in INS1-E cells and human islets. PMID: 29727907
16. Targeting oncogenic IL7R in esophageal squamous cell carcinoma (ESCC) by HDAC inhibitors via FOXO1 acetylation and repression at the IL7R promoter. PMID: 29749437
17. FOXO1 gene rearrangements in malignant ectomesenchymoma with alveolar rhabdomyosarcoma subtype. PMID: 28994342
18. HIF1alpha-induced expression of Runx2 and ALP's dependence on FOXO1 expression levels, and osteocalcin's partial dependence on FOXO1. PMID: 29512721
19. A novel role of FOXO1 inhibition in promoting IPC differentiation of hESCs. PMID: 29157981
20. FOXO1 overexpression's increase in microvilli length on cell surfaces. PMID: 30001537
21. Association of high FOXO1 expression with prostatic cancer. PMID: 29328406
22. FOXO1 as a key regulator of acquired lapatinib resistance in HER2-positive gastric cancer (GC) cells via negative crosstalk between HER2 and MET signaling pathways. PMID: 28343375
23. LncRNA DANCR's inhibition of osteoblast differentiation by regulating FOXO1 expression. PMID: 29338713
24. Correlation between physical activity level and peripheral blood mononuclear cell SIRT1 and FOXO1 mRNA expression in COPD patients. PMID: 29138552
25. FOXO1's inhibition of gastric cancer (GC) growth and angiogenesis under hypoxic conditions via inactivation of the HIF-1alpha-VEGF pathway, possibly in association with SIRT1. PMID: 25761483
26. Liraglutide's renoprotective effect via FoxO1-mediated upregulation of renal MnSOD expression in early diabetic kidney disease (DKD). PMID: 29355652
27. FOXO1 acetylation and its interaction with Atg7's regulation of basal and serum starvation-induced autophagy. PMID: 29466794
28. PAX3-FOXO1 fusion protein as a driver mutation initiating a cascade of mRNA and miRNA changes leading to alveolar rhabdomyosarcoma formation. PMID: 27588498
29. Induction of FOXO1 nuclear accumulation. PMID: 28821161
30. Akt2 ablation's protection against cardiac aging through restored Foxo1-related autophagy and mitochondrial integrity. PMID: 28681509
31. Upregulation of miR-196a in human liver cancer cells and its downregulation's impact on liver cancer cell biological functions. PMID: 28791406
32. FOXO1 inhibition's enhancement of angiogenesis in human bio-engineered capillaries, leading to microvascular regeneration. PMID: 28711779
33. PAX3-FOXO1's dependence on the BET bromodomain protein BRD4 and susceptibility to BRD inhibition. PMID: 28446439
34. FOXO1's distinct roles in promoting viability and controlled motility of adrenocortical cells. PMID: 28641336
35. FOXO1's potential role in folliculogenesis. PMID: 28621049
36. MiR-223's maintenance of breast cancer cell proliferation through targeting FOXO1. PMID: 28719355
37. MEG3's regulation of E-cadherin and FOXO1 expression by competitively binding miR-9, and its potential as a biomarker in ESCC. PMID: 28539329
38. AMPK's activation of ORP150 through the FOXO1 pathway and protection against ER stress-induced apoptosis. PMID: 29448096
39. LAT1-NAD+-SIRT1 signaling activation in non-small cell lung cancer and NAD+'s regulation of the SIRT1-FOXO1 apoptotic pathway in response to NQO1. PMID: 27566573
40. FOXO4's, but not FOXO1's, impact on proteasome activity in HD-iPSC-derived NPCs. PMID: 28973411
41. Formation of novel topologically associating domains (TADs) upon PAX3-FOXO1 translocation. PMID: 28615069
42. MALAT1's promotion of proliferation and migration by suppressing miR-26a-5p in OS cells, with FOXO1 negatively regulating MALAT1. PMID: 28160461
43. MiR-145's suppression of STAT3 phosphorylation and increased foxo1 promoter transcriptional activity. PMID: 28223425
44. KLF4's transcriptional repression of FOXO1 expression contributing to glioma cell invasion and growth. PMID: 27835585
45. FOXO1's reversal of epithelial-to-mesenchymal transition in hepatocellular carcinoma via transcription inducers Snail, Slug, ZEB1, ZEB2, and Twist1. PMID: 27924058
46. Elevated miR-425 in inflammatory bowel disease (IBD) mediating pathogenic Th17 cell generation through FOXO1 downregulation. PMID: 29331376
47. MiR-181a2/181b2's tumor suppressor ability by depressing PIK3R3 and modulating the PIK3R3/Akt/FoxO signaling pathway. PMID: 27503199
48. Association of a high extent (>25%) of BRAF(V600E) alleles with disease outcome in papillary thyroid cancer (PTC) patients. PMID: 27688110
49. Combined gamma-irradiation and dual PI3K/mTOR inhibitor treatment causing loss of stemness and FoxO1/3 proteins in p53-proficient glioblastoma multiforme stem cells. PMID: 27448972
50. AQP9 overexpression's decrease in PI3K protein levels, leading to reduced Akt phosphorylation and increased FOXO1 protein levels. PMID: 27329843

HGNC: 3819

OMIM: 136533

KEGG: hsa:2308

STRING: 9606.ENSP00000368880

UniGene: Hs.370666