Family of transcription factors involved in anatomical development
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]
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 melanogastertranscription factor forkhead. FOXF2 is expressed in the lung and
placenta.
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]
FOXP1 (pluripotency then brain, heart and lung),
FOXP2 (widely expressed? brain; language),
FOXP3 (T cells),
FOXP4 – may be ancestrally responsible for motor learning, based on insect studies (where there's only one FoxP)[9]
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]
^Lehmann OJ, Sowden JC, Carlsson P, Jordan T, Bhattacharya SS (2003). "Fox's in development and disease". Trends in Genetics. 19 (6): 339–344.
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10.1016/S0168-9525(03)00111-2.
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^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.
PMID17522590.
S2CID31546098.
^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.
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