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Regulation of the Wilms' tumour suppressor protein transcriptional activation domain

Oncogene volume 18, pages 6546–6554 (1999)Cite this article

Abstract

The Wilms' tumour suppressor protein WT1 contains a transcriptional regulatory domain that can either activate or repress transcription depending upon its cellular environment. The mechanistic basis for this dichotomy is unclear however. Here, we dissect the transcriptional regulatory domains of WT1. We find that a region within the domain of WT1 attributed to transcriptional repression is a potent suppressor of the activation domain at several promoters and in different cell types. In vitro transcription analysis suggests that the mechanism of suppression of the activation domain occurs at the level of transcription initiation. Furthermore we find that the WT1 suppression domain is able to inhibit a heterologous activation domain when fused in cis. Dissection of this domain resulted in the delineation of a 30 amino acid region that was sufficient to confer suppression of a transcriptional activation domain both in vivo and in vitro. Additionally, we find that the WT1 transcriptional activation domain interacts with the general transcription factor TFIIB and that this interaction is not affected by the suppression domain. Taken together, these studies suggest that the suppression domain of WT1 interacts with a cosuppressor protein to mediate inhibition of the WT1 transcriptional activation domain.

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Acknowledgements

We would like to thank Rachel Davies and Nick Hastie for WT1 plasmids. Also, Andy Bannister and Tony Kouzarides for transfection reporters. We thank Tom Owen-Hughes, Neil Perkins, Joost Zomerdijk and members of the lab for comments on the manuscript. This work was funded by the Wellcome Trust (047674/Z/96/Z), Cancer Research Campaign [CRC] (SP2410/0101) and Association for International Cancer Research (98 – 39). SGE Roberts is a Research Career Development Fellow of the Wellcome Trust.

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  1. Division of Gene Expression, Department of Biochemistry, Wellcome Trust Building, University of Dundee, Dundee, DD1 5EH, UK

    Lynn M McKay, Brian Carpenter & Stefan GE Roberts

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  1. Lynn M McKay
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McKay, L., Carpenter, B. & Roberts, S. Regulation of the Wilms' tumour suppressor protein transcriptional activation domain. Oncogene 18, 6546–6554 (1999). https://doi.org/10.1038/sj.onc.1203046

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