Characterization and functional analysis of the p42Ets-1 variant of the mouse Ets-1 transcription factor
| Autor: | Dominique Stehelin, Fabrice Soncin, Frédéric Lionneton, David Baillat, Etienne Lelièvre |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Transcriptional Activation
Gene isoform Cancer Research Transcription Genetic Genetic Vectors Molecular Sequence Data Response element Glutamic Acid Biology Polymerase Chain Reaction Proto-Oncogene Protein c-ets-1 Mice Sp3 transcription factor Proto-Oncogene Proteins Genetics Consensus sequence Animals Molecular Biology Transcription factor Gene DNA Primers Binding Sites Base Sequence Proto-Oncogene Proteins c-ets Reverse Transcriptase Polymerase Chain Reaction Genetic Variation Valine Promoter DNA Neoplasm Exons TCF4 Protein-Tyrosine Kinases Molecular biology Recombinant Proteins Alternative Splicing Amino Acid Substitution Protein Binding Transcription Factors |
| Zdroj: | Oncogene. 22:9156-9164 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1207241 |
| Popis: | We have identified the mouse exon VII splice variant of the Ets-1 transcription factor. The variant is expressed in all cell lines which express ets-1, at lower levels, it is also expressed in the mouse embryo in vivo. The corresponding protein, p42Ets-1, is a transcription factor as it is able to bind to specific DNA sequences and to transactivate a bona fide ETS reporter vector. A comparison of optimal DNA-binding sites shows that p42Ets-1 binds to more various DNA sequences than p51Ets-1; p42Ets-1 recognizes the same optimal consensus sequence as p51Ets-1, but also many variations of it, mainly at base -1, which is located just prior to the GGAA/T core sequence. The binding differences were quantified by surface plasmon resonance analyses and the protein region responsible for the differences in DNA sequence recognition located in the Val280-Glu302 fragment, which is encoded by exon VII. The specific DNA-binding properties of each isoform translates into clear differences in activity, p42Ets-1 transactivates the natural VE-cadherin gene promoter through both ETS-binding site (EBS)2 and EBS4 whereas p51Ets-1 is mainly active on EBS4. Altogether, our data suggest that p42Ets-1 acts as a distinct transcription factor from p51Ets-1. |
| Databáze: | OpenAIRE |
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