- ETS transcription factor family
In the field of
molecular biology, the "ETS family" is one of the largest families of transcription factorsand is unique to metazoans. There are 27 genes in humans, 26 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 ETS family is divided into 11 subfamilies, which are listed below [cite journal |author=Gutierrez-Hartman A, Duval DL, Bradford AP |title=ETS transcription factors in endocrine systems |journal=Trends Endocrinol Metab |volume=18 |issue=4 |pages=150–8 |year=2007 |pmid=17387021 |doi=10.1016/j.tem.2007.03.002 ] :
All ETS family members are identified through a highly conserved
DNA binding domain, the ETS domain, which is a winged helix-turn-helixstructure 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.
The ETS family is present throughout the body and is involved in a wide variety of functions including the regulation of
cellular differentiation, cell cyclecontrol, 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[cite journal |author=Ida K, Kobayashi S, Taki T, Hanada R, Bessho F, Yamamori S, Sugimoto T, Ohki M, Hayashi Y |title= EWS-FLI-1 and EWS-ERG chimeric mRNAs in Ewing's sarcoma and primitive neuroectodermal tumor |journal= Int J Cancer |volume=63 |issue=4 |pages=500–4 |year=1995 |pmid=7591257 |doi= 10.1002/ijc.2910630407] . The fusion of TEL to the JAK2protein results in early pre-B acute lymphoid leukaemia [cite journal |author=Peeters P, Raynaud SD, Cools J, Wlodarska I, Grosgeorge J, Philip P, Monpoux F, Van Rompaey L, Baens M, Van den Berghe H, Marynen P |title= Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia. |journal= Blood |volume=90 |issue=7 |pages=2535–40 |year=1997 |pmid=9326218 ] .
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 [cite journal | author= Verger A, Duterque-Coquillaud M |title= When Ets transcription factors meet their partners. |journal= Bioessays |volume=24 |issue=4 |pages=362–70 |year=2002 |pmid=11948622 |doi= 10.1002/bies.10068 ] . ETS factors act as transcriptional
repressors, transcriptional activators, or both [cite journal |author= Sharrocks AD |title= The ETS-domain transcription factor family |journal= Nat Rev Mol Cell Biol |volume=2 |issue=11 |pages=827–37 |year=2001 |pmid=11715049 |doi= 10.1038/35099076 ] .
*cite journal | author= Blair DG, Athanasiou M |title= Ets and retroviruses - transduction and activation of members of the Ets oncogene family in viral oncogenesis. |journal= Oncogene |volume=19 |issue=55 |pages=6472–81 |year=2000 |pmid=11175363 |doi= 10.1038/sj.onc.1204046
*cite journal | author= Li R, Pei H, Watson DK |title= Regulation of Ets function by protein - protein interactions |journal= Oncogene |volume=19 |issue=55 |pages=6514–23 |year=2000 |pmid=11175367 |doi= 10.1038/sj.onc.1204035
*cite journal | author= Mimeault M |title= Structure-function studies of ETS transcription factors. |journal= Crit Rev Oncog |volume=11 |issue=3-4 |pages=227–53 |year=2000 |pmid=11358268
*cite journal | author= Oikawa T, Yamada T |title= Molecular biology of the Ets family of transcription factors. |journal= Gene |volume=303 |pages=11–34 |year=2003 |pmid=12559563 |doi= 10.1016/S0378-1119(02)01156-3
*cite journal | author= Sementchenko VI, Watson DK |title= Ets target genes: past, present and future. |journal= Oncogene |volume=19 |issue=55 |pages=6533–48 |year=2000 |pmid=11175369 |doi= 10.1038/sj.onc.1204034
*cite journal | author= Verger A, Duterque-Coquillaud M |title= When Ets transcription factors meet their partners. |journal= Bioessays |volume=24 |issue=4 |pages=362–70 |year=2002 |pmid=11948622 |doi= 10.1002/bies.10068
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