ETS transcription factor family
Encyclopedia
In the field of molecular biology
, the ETS (E-twenty six) family is one of the largest families of transcription factors and is unique to metazoans. There are 29 genes in humans, 28 in the mouse, 10 in Caenorhabditis elegans
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.
structure that binds to DNA sites with a central GGA 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.
, cell cycle
control, cell migration
, cell proliferation, apoptosis
(programmed cell death) and angiogenesis
.
Multiple Ets factors have been found to be associated with cancer, such as through gene fusion. 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
.
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 in both C. elegans
and olfactory bulbs of mice
.
ETS factors act as transcriptional repressors, transcriptional activators, or both.
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...
, the ETS (E-twenty six) family is one of the largest families of transcription factors and is unique to metazoans. There are 29 genes in humans, 28 in the mouse, 10 in Caenorhabditis elegans
Caenorhabditis elegans
Caenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...
and 9 in Drosophila
Drosophila melanogaster
Drosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...
. 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 family is divided into 12 subfamilies, which are listed below:| Subfamily | Mammalian family members | Invertebrate orthologs |
|---|---|---|
| ELF | ELF1, ELF2 ELF2 E74-like factor 2 , also known as ELF2, is a protein which in humans is encoded by the ELF2 gene.-Further reading:... (NERF), ELF4 ELF4 ETS-related transcription factor Elf-4 is a protein that in humans is encoded by the ELF4 gene.... (MEF) |
|
| ELG | GABPα GABPA GA-binding protein alpha chain is a protein that in humans is encoded by the GABPA gene.-Interactions:GABPA has been shown to interact with Host cell factor C1, Sp1 transcription factor and Sp3 transcription factor.-External links:... |
ELG |
| ERG | ERG ERG (gene) Transcriptional regulator ERG is a protein that in humans is encoded by the ERG gene . ERG is a member of the ETS family of transcription factors.- Function :... , FLI1 FLI1 Friend leukemia integration 1 transcription factor , also known as proto-oncogene Fli-1 or transcription factor ERGB, is a protein that in humans is encoded by the human FLI1 gene. - Function :... , FEV |
|
| ERF | ERF (PE2), ETV3 (PE1) | |
| ESE | ELF3 (ESE1/ESX), ELF5 ELF5 E74-like factor 5 , is a gene found in both mice and humans. In humans it is also called ESE2.-Further reading:... (ESE2), ESE3 EHF (gene) ETS homologous factor is a protein that in humans is encoded by the EHF gene.... (EHF) |
|
| ETS | ETS1 ETS1 Protein C-ets-1 is a protein that in humans is encoded by the ETS1 gene. The protein encoded by this gene belongs to the ETS family of transcription factors.-Interactions:ETS1 has been shown to interact with TTRAP, UBE2I and Death associated protein 6.... , ETS2 ETS2 Protein C-ets-2 is a protein that in humans is encoded by the ETS2 gene. The protein encoded by this gene belongs to the ETS family of transcription factors.-Interactions:... |
POINTED |
| PDEF | SPDEF SPDEF SAM pointed domain-containing Ets transcription factor is a protein that in humans is encoded by the SPDEF gene.-Further reading:... (PDEF/PSE) |
|
| PEA3 | ETV4 ETV4 ETS translocation variant 4 is a protein that in humans is encoded by the ETV4 gene.... (PEA3/E1AF), ETV5 (ERM), ETV1 ETV1 ETS translocation variant 1 is a protein that in humans is encoded by the ETV1 gene.... (ER81) |
|
| ER71 | ETV2 ETV2 ETV2 is an Estonian television channel, transmitted in digital format.ETV2 began broadcasting on 8 August 2008, coinciding with the Olympic Games. On 25 August 2008, ETV2 continued broadcasting children's programs... (ER71) |
|
| SPI | SPI1 SPI1 Transcription factor PU.1 is a protein that in humans is encoded by the SPI1 gene.-Interactions:SPI1 has been shown to interact with NONO, GATA2, FUS and IRF4.-See also:*Invasion gene associated RNA , a ncRNA located in the SPI-1 region... (PU.1), SPIB SPIB Transcription factor Spi-B is a protein that in humans is encoded by the SPIB gene.-Interactions:SPIB has been shown to interact with MAPK3 and MAPK8.... , SPIC |
|
| TCF | ELK1 ELK1 E twenty-six -like transcription factor 1, also known as Elk1, functions as a transcription activator. It is classified as a ternary complex factor , a subclass of the ETS family, which is characterized by a common protein domain that regulates DNA binding to target sequences... , ELK4 ELK4 ETS domain-containing protein Elk-4 is a protein that in humans is encoded by the ELK4 gene.-Interactions:ELK4 has been shown to interact with Serum response factor and BRCA1.-Further reading:... (SAP1), ELK3 ELK3 ETS domain-containing protein Elk-3 is a protein that in humans is encoded by the ELK3 gene.... (NET/SAP2) |
LIN |
| TEL | ETV6 ETV6 ETV6 is an oncogene.-Interactions:ETV6 has been shown to interact with Grb2, FLI1 and HTATIP.-See also:* TEL-JAK2Mouse Mutant Alleles for Etv6 Marker Symbol for Mouse Gene. This symbol is assigned to the genomic locus by the... (TEL), ETV7 ETV7 Transcription factor ETV7 is a protein that in humans is encoded by the ETV7 gene.-External links:*... (TEL2) |
YAN |
Structure
All ETS family members are identified through a highly conserved DNA binding domain, the ETS domain, which is a winged helix-turn-helixHelix-turn-helix
In proteins, the helix-turn-helix is a major structural motif capable of binding DNA. It is composed of two α helices joined by a short strand of amino acids and is found in many proteins that regulate gene expression...
structure that binds to DNA sites with a central GGA 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 differentiationCellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
, cell cycle
Cell cycle
The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...
control, cell migration
Cell migration
Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular directions to specific locations...
, cell proliferation, apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
(programmed cell death) and angiogenesis
Angiogenesis
Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...
.
Multiple Ets factors have been found to be associated with cancer, such as through gene fusion. 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
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
.
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 in both C. elegans
Caenorhabditis elegans
Caenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...
and olfactory bulbs of mice
MICE
-Fiction:*Mice , alien species in The Hitchhiker's Guide to the Galaxy*The Mice -Acronyms:* "Meetings, Incentives, Conferencing, Exhibitions", facilities terminology for events...
.
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 is one way in which specific binding to DNA is achieved.ETS factors act as transcriptional repressors, transcriptional activators, or both.