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Ets oncogene family
1Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Abstract:
First member of Ets gene family was discovered a decade ago by studying avian erythroblastosis virus, E26. This virus encodes a tripartite protein gag-myb-ets with a molecular weight of 135 kDa. Subsequently, a series of cellular Ets genes were isolated (Ets-1, Ets-2, Erg, Elk-1, Sap-1, PEA-3, PU.1, Fli-1, Pok/Yan, Etv-1 etc.). These genes share sequence homology to E26 Ets gene (v-ets or viral ets). Ets genes are highly conserved in phylogenetically divergent species from Drosophila to man. Mammalian Ets genes are located on different chromosomes. Ets gene products are transcriptionally active sequence-specific DNA binding proteins and are differentially regulated. Ets genes are involved in certain chromosomal translocations leading to the formation of chimeric fusion proteins that are associated with certain leukemias and soft tissue cancers. Ets genes also have a role in T-cell development and molecular and genetic analysis of Down Syndrome patients have implicated the human Ets-2 and Erg genes in the disease. Down Syndrome afflicted patients have immunologic and thymic disorders as well as a greater risk for leukemic disease. Thus, Ets genes having homology to viral oncogenes, may be instrumental in regulating cellular growth and differentiation, as well as organismal development. Alteration of these genes and their products may cause deregulation of normal cell growth and differentiation and result in a disease.
Insights
The Ets gene family, discovered from avian erythroblastosis virus, includes conserved genes crucial for cellular growth and differentiation. Dysregulation of Ets genes is linked to cancers and developmental disorders like Down Syndrome.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- The Ets gene family was first identified through the avian erythroblastosis virus E26, which encodes a gag-myb-ets protein.
- Numerous cellular Ets genes (e.g., Ets-1, Ets-2, Erg, Fli-1) have since been isolated, sharing sequence homology with the viral Ets (v-ets) gene.
- These Ets genes are highly conserved across species and encode transcription factors involved in fundamental cellular processes.
Purpose of the Study:
- To review the discovery and significance of the Ets gene family.
- To highlight the role of Ets genes in normal cellular functions and disease pathogenesis.
- To emphasize the involvement of Ets genes in cancer and developmental disorders.
Main Methods:
- Literature review of Ets gene family research.
- Analysis of sequence homology and conservation across species.
- Examination of Ets gene involvement in chromosomal translocations and diseases.
Main Results:
- Ets gene products are sequence-specific DNA-binding proteins that regulate gene expression.
- Ets genes are implicated in chromosomal translocations, forming fusion proteins associated with leukemia and soft tissue cancers.
- Ets-2 and Erg genes are linked to Down Syndrome, contributing to immunologic and thymic disorders and increased leukemia risk.
Conclusions:
- Ets genes, homologous to viral oncogenes, play a critical role in regulating cellular growth, differentiation, and development.
- Alterations in Ets genes or their products can lead to deregulation of normal cellular processes, resulting in disease.
- The Ets gene family represents a significant area of study for understanding both normal development and oncogenesis.