FOXO1

Forkhead box O1

Rendering based on PDB 3CO6.
Identifiers
Symbols FOXO1; FKH1; FKHR; FOXO1A
External IDs OMIM: 136533 MGI: 1890077 HomoloGene: 1527 GeneCards: FOXO1 Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 2308 56458
Ensembl ENSG00000150907 ENSMUSG00000044167
UniProt Q12778 Q8BPP2
RefSeq (mRNA) NM_002015.3 NM_019739.3
RefSeq (protein) NP_002006.2 NP_062713.2
Location (UCSC) Chr 13:
41.13 – 41.24 Mb		 Chr 3:
52.07 – 52.15 Mb
PubMed search [1] [2]

Forkhead box protein O1 (FOXO1) also known as forkhead in rhabdomyosarcoma is a protein that in humans is encoded by the FOXO1 gene.[1]

Contents

Function

FOXO1 belongs to the forkhead family of transcription factors that are characterized by a distinct fork head domain. The specific function of this gene has not yet been determined; however, it may play a role in myogenic growth and differentiation.[2] FOXO1 is essential for the maintenance of human ESC pluripotency. This function is probably mediated through direct control by FOXO1 of OCT4 and SOX2 gene expression through occupation and activation of their respective promoters (11).In hepatic cells this transcription factor seems to increase the expression of PEPCK and glycogen-6-phosphatase (the same enzymes that are blocked via the metformin/AMPK/SHP pathway). Blocking this transcription factor offers an opportunity for novel therapies for diabetes mellitus.[3] In pancreatic alpha-cells FOXO1 is important in regulating prepro-glucagon expression.[4] In pancreatic beta cells FOXO1 mediates glucagon-like peptide-1 effects on pancreatic beta-cell mass.[5]

Clinical signficance

Translocation of this gene with PAX3 has been associated with alveolar rhabdomyosarcoma.[1][6]

Interactions

FOXO1 has been shown to interact with TSC2,[7] androgen receptor,[8] estrogen receptor alpha[9] and CREB-binding protein.[10]

References

  1. ^ a b Galili N, Davis RJ, Fredericks WJ, Mukhopadhyay S, Rauscher FJ, Emanuel BS, Rovera G, Barr FG (November 1993). "Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma". Nat. Genet. 5 (3): 230–5. doi:10.1038/ng1193-230. PMID 8275086. 
  2. ^ "Entrez Gene: FOXO1 forkhead box O1 (rhabdomyosarcoma)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2308. 
  3. ^ Nagashima T, Shigematsu N, Maruki R, Urano Y, Tanaka H, Shimaya A, Shimokawa T, Shibasaki M (August 2010). "Discovery of novel Foxo1 inhibitors for treating type 2 diabetes: Improvement of fasting glycemia in diabetic db/db mice". Mol Pharmacol 78 (5): 961. doi:10.1124/mol.110.065714. PMID 20736318. 
  4. ^ McKinnon CM, Ravier MA, Rutter GA (December 2006). "FoxO1 is required for the regulation of preproglucagon gene expression by insulin in pancreatic alphaTC1-9 cells". J. Biol. Chem. 281 (51): 39358–69. doi:10.1074/jbc.M605022200. PMID 17062568. 
  5. ^ Buteau J, Spatz ML, Accili D (May 2006). "Transcription factor FoxO1 mediates glucagon-like peptide-1 effects on pancreatic beta-cell mass". Diabetes 55 (5): 1190–6. doi:10.2337/db05-0825. PMID 16644672. 
  6. ^ Linardic CM (October 2008). "PAX3-FOXO1 fusion gene in rhabdomyosarcoma". Cancer Lett. 270 (1): 10–8. doi:10.1016/j.canlet.2008.03.035. PMC 2575376. PMID 18457914. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2575376. 
  7. ^ Cao Y, Kamioka Y, Yokoi N, Kobayashi T, Hino O, Onodera M, Mochizuki N, Nakae J (December 2006). "Interaction of FoxO1 and TSC2 induces insulin resistance through activation of the mammalian target of rapamycin/p70 S6K pathway". J. Biol. Chem. 281 (52): 40242–51. doi:10.1074/jbc.M608116200. PMID 17077083. 
  8. ^ Li P, Lee H, Guo S, Unterman TG, Jenster G, Bai W (January 2003). "AKT-independent protection of prostate cancer cells from apoptosis mediated through complex formation between the androgen receptor and FKHR". Mol. Cell. Biol. 23 (1): 104–18. doi:10.1128/MCB.23.1.104-118.2003. PMC 140652. PMID 12482965. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=140652. 
  9. ^ Schuur ER, Loktev AV, Sharma M, Sun Z, Roth RA, Weigel RJ (September 2001). "Ligand-dependent interaction of estrogen receptor-alpha with members of the forkhead transcription factor family". J. Biol. Chem. 276 (36): 33554–60. doi:10.1074/jbc.M105555200. PMID 11435445. 
  10. ^ Nasrin N, Ogg S, Cahill CM, Biggs W, Nui S, Dore J, Calvo D, Shi Y, Ruvkun G, Alexander-Bridges MC (September 2000). "DAF-16 recruits the CREB-binding protein coactivator complex to the insulin-like growth factor binding protein 1 promoter in HepG2 cells". Proc. Natl. Acad. Sci. U.S.A. 97 (19): 10412–7. doi:10.1073/pnas.190326997. PMC 27038. PMID 10973497. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=27038. 

(11) Xin Zhang et al., & Saghi Ghaffari (2011) FOXO1 is an essential regulator of pluripotency

     in     human embryonic stem cells   Nature Cell Biology  doi:10.1038/ncb2293

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.