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FOX proteins: Wikis


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FOX (Forkhead box) proteins are a family of transcription factors that play important roles in regulating the expression of genes involved in cell growth, proliferation, differentiation, and longevity. Many FOX proteins are important to embryonic development.[1][2]

The defining feature of FOX proteins is the forkhead box, a sequence of 80 to 100 amino acids forming a motif that binds to DNA. This forkhead motif is also known as the winged helix due to the butterfly-like appearance of the loops in the protein structure of the domain.[3] Forkhead genes are a subgroup of the helix-turn-helix class of proteins.


Biological roles

Many other genes encoding FOX proteins have been identified. For example, the FOXF2 gene encodes forkhead box F2, one of many human homologues of the Drosophila melanogaster transcription factor forkhead. FOXF2 is expressed in lung and placenta.

Some FOX genes are downstream targets of the hedgehog signaling pathway, which plays a role in the development of basal cell carcinomas. Members of the class O regulate metabolism, cellular proliferation, stress tolerance and probably lifespan. The activity of FoxO is controlled by post-translational modifications, including phosphorylation, acetylation and ubiquitylation.[4]


The first protein in the FOX family that was discovered was the fork head transcription factor in Drosophila (thus the name). Since then a large number of family members have been discovered, especially in vertebrates. Originally they were given vastly different names (such as HFH, FREAC, and fkh), but in 2000 a unified nomenclature was introduced that grouped the FOX proteins into subclasses (FOXA-FOXS) based on sequence conservation.[5]



  1. ^ Tuteja G, Kaestner KH (September 2007). "SnapShot: forkhead transcription factors I". Cell 130 (6): 1160. doi:10.1016/j.cell.2007.09.005. PMID 17889656.  
  2. ^ Tuteja G, Kaestner KH (October 2007). "Forkhead transcription factors II". Cell 131 (1): 192. doi:10.1016/j.cell.2007.09.016. PMID 17923097.  
  3. ^ Lehmann OJ, Sowden JC, Carlsson P, Jordan T, Bhattacharya SS (2003). "Fox's in development and disease". TRENDS in Genetics 19 (6): 339–344. doi:10.1016/S0168-9525(03)00111-2. PMID 12801727.  
  4. ^ van der Horst A, Burgering BM (June 2007). "Stressing the role of FoxO proteins in lifespan and disease". Nat. Rev. Mol. Cell Biol. 8 (6): 440–50. doi:10.1038/nrm2190. PMID 17522590.  
  5. ^ Kaestner KH, Knochel W, Martinez DE (2000). "Unified nomenclature for the winged helix/forkhead transcription factors". Genes and Development 14: 142–146. PMID 10702024.  

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