In the field ofmolecular biology, theETS (E26 transformation-specific[2] orErythroblast Transformation Specific[3])family is one of the largest families oftranscription factors and is unique toanimals. There are 28genes in humans,[4] 27 in the mouse, 10 inCaenorhabditis elegans and 9 inDrosophila. 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.
All ETS (Erythroblast Transformation Specific) family members are identified through a highly conservedDNA binding domain, theETS domain, which is a wingedhelix-turn-helix structure that binds to DNA sites with a centralGGA(A/T) DNA sequence. As well as DNA-binding functions, evidence suggests that the ETS domain is also involved inprotein-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.
Multiple ETS factors have been found to be associated with cancer, such as throughgene fusion. For example, theERG ETS transcription factor is fused to theEWS gene, resulting in a condition calledEwing's sarcoma.[6] The fusion ofTEL to theJAK2 protein results in early pre-B acute lymphoid leukaemia.[7] ERG and ETV1 are known gene fusions found inprostate cancer.[8]
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 ofdopaminergic neurons in bothC. elegans andolfactory bulbs ofmice.[9]
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.[10]ETS factors act as transcriptionalrepressors,transcriptional activators, or both.[11]
^Leprince, D.; Gegonne, A.; Coll, J.; De Taisne, C.; Schneeberger, A.; Lagrou, C.; Stehelin, D. (1983). "A putative second cell-derived oncogene of the avian leukaemia retrovirus E26".Nature.306 (5941):395–397.Bibcode:1983Natur.306..395L.doi:10.1038/306395a0.PMID6316156.S2CID4318034.
^Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, Varambally S, Cao X, Tchinda J, Kuefer R, Lee C, Montie JE, Shah RB, Pienta KJ, Rubin MA, Chinnaiyan AM (October 2005). "Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer".Science.310 (5748):644–8.Bibcode:2005Sci...310..644T.doi:10.1126/science.1117679.PMID16254181.S2CID85788789.
^Verger A, Duterque-Coquillaud M (2002). "When Ets transcription factors meet their partners".BioEssays.24 (4):362–70.doi:10.1002/bies.10068.PMID11948622.
Verger A, Duterque-Coquillaud M (2002). "When Ets transcription factors meet their partners".BioEssays.24 (4):362–70.doi:10.1002/bies.10068.PMID11948622.
