The pro-oncoprotein EWS (Ewing's Sarcoma protein) interacts with the Brn-3a POU transcription factor and inhibits its ability to activate transcription.
The Brn-3a POU family transcription factor is able to induce the expression of a number of neuronally-expressed genes as well as to enhance neuronal differentiation and inhibit apoptosis. Many of these effects are mediated by the C-terminal POU domain of Brn-3a which acts both as a DNA binding domain and a transcriptional activation domain. To identify the mechanisms by which this domain acts, we carried out a yeast two hybrid assay to identify proteins which interact with it. We show that both full length Brn-3a and the isolated POU domain interact with the EWS transcription factor and its oncogenic derivative EWS-Fli1. Moreover, EWS can block Brn-3a-mediated activation of the Bcl-x promoter whereas this effect is lost in EWS-Fli1. The significance of this novel interaction is discussed in terms of the manner in which Brn-3a regulates its target promoters and the mechanism of oncogenic transformation by EWS-Fli1.
Thomas
G Ruth
GR
Medical Molecular Biology Unit, Institute of Child Health, University College London, UK.
Latchman
David S
DS
D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000378:metabolism*; D017930:Genes, Reporter; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D034802:RNA-Binding Protein EWS / Q000378:metabolism*; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
D004268:DNA-Binding Proteins; C494188:POU4F1 protein, human; D034802:RNA-Binding Protein EWS; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D014157:Transcription Factors; D008156:Luciferases; D005982:Glutathione Transferase