ETS transcription factor family
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In the field of molecular biology, the ETS family is one of the largest families of transcription factors and 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.
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[edit] Subfamilies
The ETS family is divided into 11 subfamilies, which are listed below[1]:
| Subfamily | Members and their homologs |
|---|---|
| ELF | ELF1, NERF/ELF2, MEF/ELF4 |
| ELG | GABPα, ELG |
| ERG | ERG, FLI1, FEV |
| ERF | ERF/PE2, ETV3/PE1 |
| ESE | ESE1/ESX/ELF3, ESE2/ELF5, ESE3/EHF |
| ETS | ETS1, ETS2, POINTED |
| PDEF | PDEF/SPDEF/PSE |
| PEA3 | PEA3/E1AF/ETV4, ERM/ETV5, ER81/ETV1, ER71/ETV2 |
| SPI | PU.1/SPI, SPIB, SPIC |
| TCF | ELK1, SAP1/ELK4, NET/SAP2/ELK3, LIN |
| TEL | TEL/ETV6, TEL2/ETV7, YAN |
[edit] Structure
All ETS family members are identified through a highly conserved DNA binding domain, the ETS domain, which is a winged helix-turn-helix 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.
[edit] Function
The ETS family is present throughout the body and is involved in a wide variety of functions including the regulation of cellular differentiation, 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[2]. The fusion of TEL to the JAK2 protein results in early pre-B acute lymphoid leukaemia[3].
[edit] 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[4]. ETS factors act as transcriptional repressors, transcriptional activators, or both[5].
[edit] References
- ^ Gutierrez-Hartman A, Duval DL, Bradford AP (2007). "ETS transcription factors in endocrine systems". Trends Endocrinol Metab 18 (4): 150–8. doi:. PMID 17387021.
- ^ Ida K, Kobayashi S, Taki T, Hanada R, Bessho F, Yamamori S, Sugimoto T, Ohki M, Hayashi Y (1995). "EWS-FLI-1 and EWS-ERG chimeric mRNAs in Ewing's sarcoma and primitive neuroectodermal tumor". Int J Cancer 63 (4): 500–4. doi:. PMID 7591257.
- ^ 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 (1997). "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.". Blood 90 (7): 2535–40. PMID 9326218.
- ^ Verger A, Duterque-Coquillaud M (2002). "When Ets transcription factors meet their partners.". Bioessays 24 (4): 362–70. doi:. PMID 11948622.
- ^ Sharrocks AD (2001). "The ETS-domain transcription factor family". Nat Rev Mol Cell Biol 2 (11): 827–37. doi:. PMID 11715049.
[edit] Further reading
- Blair DG, Athanasiou M (2000). "Ets and retroviruses - transduction and activation of members of the Ets oncogene family in viral oncogenesis.". Oncogene 19 (55): 6472–81. doi:. PMID 11175363.
- Li R, Pei H, Watson DK (2000). "Regulation of Ets function by protein - protein interactions". Oncogene 19 (55): 6514–23. doi:. PMID 11175367.
- Mimeault M (2000). "Structure-function studies of ETS transcription factors.". Crit Rev Oncog 11 (3-4): 227–53. PMID 11358268.
- Oikawa T, Yamada T (2003). "Molecular biology of the Ets family of transcription factors.". Gene 303: 11–34. doi:. PMID 12559563.
- Sementchenko VI, Watson DK (2000). "Ets target genes: past, present and future.". Oncogene 19 (55): 6533–48. doi:. PMID 11175369.
- Verger A, Duterque-Coquillaud M (2002). "When Ets transcription factors meet their partners.". Bioessays 24 (4): 362–70. doi:. PMID 11948622.
