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PRCC, the commonest TFE3 fusion partner in papillary renal carcinoma is associated with pre-mRNA splicing factors

Oncogene volume 20, pages 178–187 (2001)Cite this article

Abstract

In papillary renal cell carcinomas the TFE3 transcription factor becomes fused to the PSF and NonO pre-mRNA splicing factors and most commonly to a protein of unknown function designated PRCC. In this study we have examined the ability of the resulting PRCC–TFE3 and NonO–TFE3 fusions to activate transcription from the plasminogen activator inhibitor-1 (PAI-1) promoter. The results show that only fusion to PRCC enhanced transcriptional activation, indicating that the ability to enhance the level of transcription from endogenous TFE3 promoters is not a consistent feature of TFE3 fusions. In investigations of the normal function of PRCC we observed that PRCC expressed as a green fluorescent fusion protein colocalizes within the nucleus with Sm pre-mRNA splicing factors. It was also found that endogenous PRCC is coimmunoprecipitated by antibodies that recognize a variety of pre-mRNA splicing factors including SC35, PRL1 and CDC5. Association with the cellular splicing machinery is therefore, a common feature of the proteins that become fused to TFE3 in papillary renal cell carcinomas.

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Acknowledgements

AI Lamond and PM Ajuh are supported by the Wellcome Trust and AI Lamond is a Wellcome Trust Principal Research Fellow. YM Skalsky is funded by the Cancer Research Campaign. We also thank Dr Xianxin H for providing PE2 and PmE2 plasmids and Dr C Hill for providing SMAD3 plasmid, S Gill for cell lines and RNAs, L Trinkle-Mulcahy for helpful discussions, and particularly to J Clark for helpful discussions and assistance all along this work. We also thank all members of our laboratory Claudia Michela and Kammedea for technical assistance and Sally Townsand for typing the manuscript.

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  1. Institute of Cancer Research, Molecular Carcinogenesis Section, The Haddow Laboratories, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK

    Y M Skalsky, C Parker, G Goodwin & C S Cooper

  2. Department of Biochemistry, The University of Dundee, MSI/WTB Complex, Dow Street, Dundee, DD1 5EH, UK

    P M Ajuh & A I Lamond

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  1. Y M Skalsky
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Skalsky, Y., Ajuh, P., Parker, C. et al. PRCC, the commonest TFE3 fusion partner in papillary renal carcinoma is associated with pre-mRNA splicing factors. Oncogene 20, 178–187 (2001). https://doi.org/10.1038/sj.onc.1204056

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