FOX proteins

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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] FOX proteins also have pioneering transcription activity by being able to bind condensed chromatin during cell differentiation processes. [3]

Contents

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. [4] Forkhead proteins are a subgroup of the helix-turn-helix class of proteins.

Biological roles

Many 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 the 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 class O (FOXO- proteins) regulate metabolism, cellular proliferation, stress tolerance and possibly lifespan. The activity of FoxO is controlled by post-translational modifications, including phosphorylation, acetylation and ubiquitination. [5]

Discovery

The founding member and namesake of the FOX family is the fork head transcription factor in Drosophila, discovered by German biologists Detlef Weigel and Herbert Jäckle. [6] [7] 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. [8]

Genes

Cancer

A member of the FOX family, FOXD2, has been detected progressively overexpressed in human-papillomavirus-positive neoplastic keratinocytes derived from uterine cervical preneoplastic lesions at different levels of malignancy. [11] For this reason, this gene is likely to be associated with tumorigenesis and may be a potential prognostic marker for uterine cervical preneoplastic lesions progression. [11]

Related Research Articles

<span class="mw-page-title-main">FOXP3</span> Immune response protein

FOXP3, also known as scurfin, is a protein involved in immune system responses. A member of the FOX protein family, FOXP3 appears to function as a master regulator of the regulatory pathway in the development and function of regulatory T cells. Regulatory T cells generally turn the immune response down. In cancer, an excess of regulatory T cell activity can prevent the immune system from destroying cancer cells. In autoimmune disease, a deficiency of regulatory T cell activity can allow other autoimmune cells to attack the body's own tissues.

<span class="mw-page-title-main">FOXC2</span> Protein-coding gene in the species Homo sapiens

Forkhead box protein C2 (FOXC2) also known as forkhead-related protein FKHL14 (FKHL14), transcription factor FKH-14, or mesenchyme fork head protein 1 (MFH1) is a protein that in humans is encoded by the FOXC2 gene. FOXC2 is a member of the fork head box (FOX) family of transcription factors.

Hepatocyte nuclear factors (HNFs) are a group of phylogenetically unrelated transcription factors that regulate the transcription of a diverse group of genes into proteins. These proteins include blood clotting factors and in addition, enzymes and transporters involved with glucose, cholesterol, and fatty acid transport and metabolism.

<span class="mw-page-title-main">FOXP1</span> Protein-coding gene in the species Homo sapiens

Forkhead box protein P1 is a protein that in humans is encoded by the FOXP1 gene. FOXP1 is necessary for the proper development of the brain, heart, and lung in mammals. It is a member of the large FOX family of transcription factors.

<span class="mw-page-title-main">FOXO3</span> Protein-coding gene in the species Homo sapiens

Forkhead box O3, also known as FOXO3 or FOXO3a, is a human protein encoded by the FOXO3 gene.

<span class="mw-page-title-main">Forkhead box C1</span> Protein-coding gene in the species Homo sapiens

Forkhead box C1, also known as FOXC1, is a protein which in humans is encoded by the FOXC1 gene.

<span class="mw-page-title-main">FOXO4</span> Protein

Forkhead box protein O4 is a protein that in humans is encoded by the FOXO4 gene.

<span class="mw-page-title-main">FOXL2</span> Transcription factor gene of the FOX family

Forkhead box protein L2 is a protein that in humans is encoded by the FOXL2 gene.

<span class="mw-page-title-main">FOXP4</span> Human protein-coding gene

Forkhead box protein P4 is a protein that in humans is encoded by the FOXP4 gene.

<span class="mw-page-title-main">FOXD4</span> Protein-coding gene in the species Homo sapiens

Forkhead box protein D4 is a protein that in humans is encoded by the FOXD4 gene.

<span class="mw-page-title-main">FOXN1</span> Protein-coding gene in the species Homo sapiens

Forkhead box protein N1 is a protein that in humans is encoded by the FOXN1 gene.

<span class="mw-page-title-main">Fork head domain</span> DNA-binding protein domain found in transcription factors

The fork head domain is a type of protein domain that is often found in transcription factors and whose purpose is to bind DNA.

<span class="mw-page-title-main">Forkhead box protein O1</span> Protein

Forkhead box protein O1 (FOXO1), also known as forkhead in rhabdomyosarcoma (FKHR), is a protein that in humans is encoded by the FOXO1 gene. FOXO1 is a transcription factor that plays important roles in regulation of gluconeogenesis and glycogenolysis by insulin signaling, and is also central to the decision for a preadipocyte to commit to adipogenesis. It is primarily regulated through phosphorylation on multiple residues; its transcriptional activity is dependent on its phosphorylation state.

<span class="mw-page-title-main">FOXA1</span> Protein-coding gene in the species Homo sapiens

Forkhead box protein A1 (FOXA1), also known as hepatocyte nuclear factor 3-alpha (HNF-3A), is a protein that in humans is encoded by the FOXA1 gene.

<span class="mw-page-title-main">FOXA2</span> Mammalian protein found in Homo sapiens

Forkhead box protein A2 (FOXA2), also known as hepatocyte nuclear factor 3-beta (HNF-3B), is a transcription factor that plays an important role during development, in mature tissues and, when dysregulated or mutated, also in cancer.

<span class="mw-page-title-main">FOXA3</span> Protein-coding gene in the species Homo sapiens

Hepatocyte nuclear factor 3-gamma (HNF-3G), also known as forkhead box protein A3 (FOXA3) or transcription factor 3G (TCF-3G) is a protein that in humans is encoded by the FOXA3 gene.

<span class="mw-page-title-main">FOXI1</span> Protein-coding gene in the species Homo sapiens

Forkhead box I1 is a protein that in humans is encoded by the FOXI1 gene.

<span class="mw-page-title-main">FOXJ1</span> Protein-coding gene in the species Homo sapiens

Forkhead box protein J1 is a protein that in humans is encoded by the FOXJ1 gene. It is a member of the Forkhead/winged helix (FOX) family of transcription factors that is involved in ciliogenesis. FOXJ1 is expressed in ciliated cells of the lung, choroid plexus, reproductive tract, embryonic kidney and pre-somite embryo stage.

<span class="mw-page-title-main">Forkhead box d1</span> Human protein-coding gene

Forkhead box D1 is a protein that in humans is encoded by the FOXD1 gene. Forkhead d1 is a kidney expressed transcription factor maps at the chromosome 5 at position 5q12—q13, identified in Drosophila forkhead protein and mammalian HNF3 transcription factor. The name of was derived from two spiked head structures in the embryos of Drosophila forkhead mutant. It belong to transcription factor family that displays remarkable functional diversity and involved in a wide variety of biological processes. The most commonly used synonyms for Forkhead D1 are, FOX D1, FREAC-4 and BF2.

<span class="mw-page-title-main">FOXO6</span> Protein-coding gene in the species Homo sapiens

Forkhead box O6 is a protein that in humans is encoded by the FOXO6 gene.

References

  1. ↑ Tuteja G, Kaestner KH (September 2007). "SnapShot: forkhead transcription factors I". Cell. 130 (6): 1160.e1–1160.e2. doi: 10.1016/j.cell.2007.09.005 . PMID   17889656. S2CID   38793380.
  2. ↑ Tuteja G, Kaestner KH (October 2007). "Forkhead transcription factors II". Cell. 131 (1): 192–192.e1. doi: 10.1016/j.cell.2007.09.016 . PMID   17923097. S2CID   322449.
  3. ↑ Zaret KS, Carroll JS (November 2011). "Pioneer transcription factors: establishing competence for gene expression". Genes Dev. 25 (21): 2227–41. doi:10.1101/gad.176826.111. PMC   3219227 . PMID   22056668.
  4. ↑ 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.
  5. ↑ 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. S2CID   31546098.
  6. ↑ Weigel D, Jürgens G, Küttner F, Seifert E, Jäckle H (1989). "The homeotic gene fork head encodes a nuclear protein and is expressed in the terminal regions of the Drosophila embryo". Cell. 57 (4): 645–658. doi:10.1016/0092-8674(89)90133-5. PMID   2566386. S2CID   12317967.
  7. ↑ Weigel D, Jäckle H (1990). "The fork head domain, a novel DNA-binding motif of eucaryotic transcription factors?". Cell. 63 (3): 455–456. doi:10.1016/0092-8674(90)90439-L. PMID   2225060. S2CID   1986657.
  8. ↑ Kaestner KH, Knochel W, Martinez DE (2000). "Unified nomenclature for the winged helix/forkhead transcription factors". Genes & Development. 14 (2): 142–146. doi: 10.1101/gad.14.2.142 . PMID   10702024. S2CID   26488600.
  9. ↑ Mendoza, E; Colomb, J; Rybak, J; Pflüger, HJ; Zars, T; Scharff, C; Brembs, B (2014). "Drosophila FoxP mutants are deficient in operant self-learning". PLOS ONE. 9 (6): e100648. Bibcode:2014PLoSO...9j0648M. doi: 10.1371/journal.pone.0100648 . PMC   4070984 . PMID   24964149.
  10. ↑ "Gene group: Forkhead boxes (FOX)". HUGO Gene Nomenclature Committee at the European Bioinformatics Institute. Retrieved 6 June 2021.
  11. 1 2 Rotondo JC, Bosi S, Bassi C, Ferracin M, Lanza G, Gafà R, Magri E, Selvatici R, Torresani S, Marci R, Garutti P, Negrini M, Tognon M, Martini F (April 2015). "Gene expression changes in progression of cervical neoplasia revealed by microarray analysis of cervical neoplastic keratinocytes". J Cell Physiol. 230 (4): 802–812. doi:10.1002/jcp.24808. hdl: 11392/2066612 . PMID   25205602. S2CID   24986454.
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