FOX (forkhead box) proteins are a family of
transcription factors that play important roles in regulating the expression of
genes involved in
cell growth
Cell growth refers to an increase in the total mass of a cell, including both cytoplasmic, nuclear and organelle volume. Cell growth occurs when the overall rate of cellular biosynthesis (production of biomolecules or anabolism) is greater than ...
, proliferation,
differentiation, and
longevity
The word " longevity" is sometimes used as a synonym for "life expectancy" in demography. However, the term ''longevity'' is sometimes meant to refer only to especially long-lived members of a population, whereas ''life expectancy'' is always d ...
. Many FOX
proteins
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
are important to embryonic development.
FOX proteins also have
pioneering transcription activity by being able to bind condensed
chromatin during cell differentiation processes.
The defining feature of FOX proteins is the
forkhead box, a sequence of 80 to 100
amino acids
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
forming a
motif
Motif may refer to:
General concepts
* Motif (chess composition), an element of a move in the consideration of its purpose
* Motif (folkloristics), a recurring element that creates recognizable patterns in folklore and folk-art traditions
* Moti ...
that binds to
DNA. This forkhead motif is also known as the
winged helix
Consisting of about 110 amino acids, the domain in winged-helix transcription factors (see Regulation of gene expression) has four helices and a two-strand beta-sheet.
These proteins are classified into 19 families called FoxA-FoxS.
Mutation ...
, due to the butterfly-like appearance of the loops in the protein structure of the domain.
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 carcinoma
Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesodermal ...
s. 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
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...
,
acetylation
:
In organic chemistry, acetylation is an organic esterification reaction with acetic acid. It introduces an acetyl group into a chemical compound. Such compounds are termed ''acetate esters'' or simply '' acetates''. Deacetylation is the oppo ...
and
ubiquitination.
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.
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.
Genes
*
FOXA1,
FOXA2,
FOXA3 (See also
Hepatocyte nuclear factors.)
*
FOXB1,
FOXB2
*
FOXC1
Forkhead box C1, also known as FOXC1, is a protein which in humans is encoded by the ''FOXC1'' gene.
Function
This gene belongs to the forkhead family of transcription factors which is characterized by a distinct DNA-binding fork head dom ...
(associated with glaucoma),
FOXC2 (varicose veins)
*
FOXD1,
FOXD2,
FOXD3
Forkhead box D3 also known as FOXD3 is a forkhead protein that in humans is encoded by the ''FOXD3'' gene.
Function
This gene belongs to the forkhead protein family of transcription factors which is characterized by a DNA-binding forkhead do ...
(
vitiligo),
FOXD4
Forkhead box protein D4 is a protein that in humans is encoded by the ''FOXD4'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ' ...
,
FOXD4L1,
FOXD4L3,
FOXD4L4,
FOXD4L5,
FOXD4L6
*
FOXE1
Forkhead box protein E1 is a protein that in humans is encoded by the ''FOXE1'' gene.
Location
The FOXE1 gene is located on the long (q) arm of chromosome 9 at position 22
Function
This intronless gene belongs to the forkhead family of tran ...
(thyroid),
FOXE3 (lens)
*
FOXF1 (lung),
FOXF2
*
FOXG1 (brain)
*
FOXH1 (widely expressed)
*
FOXI1 (ear),
FOXI2,
FOXI3
*
FOXJ1 (cilia),
FOXJ2 (erythroid),
FOXJ3
*
FOXK1,
FOXK2 (HIV, IL-2, adrenal)
*
FOXL1 (ovary),
FOXL2
*
FOXM1 (cell cycle, erythroid, cancer)
*
FOXN1 (hair, thymus),
FOXN2,
FOXN3 (cell cycle checkpoints; widely expressed),
FOXN4
*
FOXO1 (widely expressed: muscle, liver, pancreas),
FOXO3 (apoptosis, erythroid, longevity),
FOXO4 (widely expressed),
FOXO6 (liver, skeletal muscle, brain)
*
FOXP1
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.
Func ...
(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'')
*
FOXQ1
Forkhead box Q1 is a protein that in humans is encoded by the FOXQ1 gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ...
*
FOXR1,
FOXR2
*
FOXS1
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.
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.
References
External links
*
{{DEFAULTSORT:Fox Proteins
*
Aging-related proteins