In the field of
molecular biology, the ETS (E26 transformation-specific or E-twenty-six. (Erythroblast Transformation Specific)) family is one of the largest families of
transcription factors and is unique to
animals. There are 29
genes
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
in humans, 28 in the mouse, 10 in ''
Caenorhabditis elegans
''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (ro ...
'' and 9 in ''
Drosophila.'' The founding member of this family was identified as a gene transduced by the leukemia virus, E26. The members of the family have been implicated in the development of different tissues as well as cancer progression.
Subfamilies
The ETS (Erythroblast Transformation Specific)family is divided into 12 subfamilies, which are listed below:
Structure
All ETS (Erythroblast Transformation Specific) family members are identified through a highly conserved
DNA binding domain
A DNA-binding domain (DBD) is an independently folded protein domain that contains at least one structural motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence (a recognition sequence) or have a genera ...
, the ETS domain, which is a winged
helix-turn-helix structure that binds to DNA sites with a central GGA(A/T) DNA sequence. As well as DNA-binding functions, evidence suggests that the ETS domain is also involved in
protein-protein interactions.
There is limited similarity outside the ETS DNA binding domain.
Other domains are also present and vary from ETS member to ETS member, including the Pointed domain, a subclass of the SAM domain family.
Function
The ETS family is present throughout the body and is involved in a wide variety of functions including the regulation of
cellular differentiation
Cellular differentiation is the process in which a stem cell alters from one type to a differentiated one. Usually, the cell changes to a more specialized type. Differentiation happens multiple times during the development of a multicellular ...
,
cell cycle control,
cell migration,
cell proliferation
Cell proliferation is the process by which ''a cell grows and divides to produce two daughter cells''. Cell proliferation leads to an exponential increase in cell number and is therefore a rapid mechanism of tissue growth. Cell proliferation re ...
,
apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
(programmed cell death) and
angiogenesis
Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting ...
.
Multiple ETS factors have been found to be associated with cancer, such as through
gene fusion A fusion gene is a hybrid gene formed from two previously independent genes. It can occur as a result of translocation, interstitial deletion, or chromosomal inversion. Fusion genes have been found to be prevalent in all main types of human neoplas ...
. For example, the ERG ETS transcription factor is fused to the EWS gene, resulting in a condition called
Ewing's sarcoma. The fusion of TEL to the
JAK2 protein results in early pre-B acute lymphoid leukaemia. ERG and ETV1 are known gene fusions found in
prostate cancer
Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...
.
In addition, ETS factors, e.g. the vertebrate Etv1 and the invertebrate Ast-1, have been shown to be important players in the specification and differentiation of
dopaminergic neurons
Dopaminergic cell groups, DA cell groups, or dopaminergic nuclei are collections of neurons in the central nervous system that synthesize the neurotransmitter dopamine. In the 1960s, dopaminergic neurons or ''dopamine neurons'' were first ident ...
in both ''
C. elegans
''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...
'' and
olfactory bulbs
The olfactory bulb (Latin: ''bulbus olfactorius'') is a neural structure of the vertebrate forebrain involved in olfaction, the sense of smell. It sends olfactory information to be further processed in the amygdala, the orbitofrontal cortex (OFC ...
of
mice
A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...
.
Mode of action
Amongst members of the ETS family, there is extensive conservation in the DNA-binding ETS domain and, therefore, a lot of redundancy in DNA binding. It is thought that interactions with other proteins (eg: Modulator of the activity of Ets called Mae) is one way in which specific binding to DNA is achieved. Transcription factor Ets are a site of signalling convergence.
ETS factors act as transcriptional
repressors
In molecular genetics, a repressor is a DNA-binding protein, DNA- or RNA-binding protein that inhibits the Gene expression, expression of one or more genes by binding to the Operator (biology), operator or associated Silencer (DNA), silencers. ...
,
transcriptional activators, or both.
References
Further reading
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{{DEFAULTSORT:Ets Transcription Factor Family
Gene expression
Transcription factors
Protein families