The Pro-Oncoprotein EWS (Ewing’s Sarcoma Protein) Interacts with the Brn-3a POU Transcription Factor and Inhibits its Ability Activate Transcription

 Abstract

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.

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Pages
428 - 432
doi
10.4161/cbt.1.4.23
Type
Research Paper
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The Pro-Oncoprotein EWS (Ewing’s Sarcoma Protein) Interacts with the Brn-3a POU Transcription Factor and Inhibits its Ability Activate Transcription