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The tumour-suppressor protein ASPP1 is nuclear in human germ cells and can modulate ratios of CD44 exon V5 spliced isoforms in vivo

Oncogene volume 25, pages 3104–3112 (2006)Cite this article

Abstract

The ASPP1 (Apoptosis Stimulating Protein of p53) protein is an important tumour-suppressor. We have detected a novel protein interaction between the human ASPP1 (hASPP1) protein and the predominantly nuclear adaptor protein SAM68. In the human testis, full-length endogenous hASPP1 protein is located in the nucleus like SAM68, predominantly within meiotic and postmeiotic cells. Mouse ASPP1 (mASPP1) protein is mainly expressed in the brain and testis. The interaction with nuclear SAM68 is likely to be restricted to human germ cells, since endogenous mASPP1 protein is exclusively cytoplasmic. The C-terminal region of hASPP1 efficiently targeted a fused GFP molecule to the nucleus, whereas the N-terminus of hASPP1 targeted GFP to the cytoplasm. In the context of the full-length molecule this cytoplasmic targeting sequence is dominant in HEK293 and Saos-2 cells, since full-length hASPP1-GFP is almost exclusively cytoplasmic. Despite its predominantly cytoplasmic location, we show that ASPP1-GFP expression in HEK293 cells can regulate the ratio of alternative spliced isoforms derived from a pre-mRNA regulated downstream of cytoplasmic signalling pathways, and our data suggest that ASPP1 may operate in this case downstream or parallel to RAS signalling pathways.

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Acknowledgements

We thank Dr Rachel Davies, Dr Mauro Santibanez Koref, Dr Sushman Nagaraj-Grellscheid and Dr Alison Trainer for their comments, Professor Julian Downward for the dominant-negative RAS construct, Professor Stefan Stamm for the CD44 minigene and Derek Hawes for help with photography. Jared Thornton was supported by a Luccock PhD studentship (University of Newcastle). Kate Sergeant is a William Ross CRUK student. This work was supported by the BBSRC, the Special Trustees of the RVI and Wellcome Trust by Project Grants to DJE.

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Authors and Affiliations

  1. Institute of Human Genetics, University of Newcastle, International Centre for Life, Central Parkway, Newcastle, UK

    J K Thornton, C Dalgleish, J P Venables, K A Sergeant, I E Ehrmann & D J Elliott

  2. Ludwig Institute for Cancer Research, University College London, London, UK

    X Lu

  3. MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, Edinburgh, UK

    P T K Saunders

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  1. J K Thornton
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Correspondence to D J Elliott.

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Thornton, J., Dalgleish, C., Venables, J. et al. The tumour-suppressor protein ASPP1 is nuclear in human germ cells and can modulate ratios of CD44 exon V5 spliced isoforms in vivo. Oncogene 25, 3104–3112 (2006). https://doi.org/10.1038/sj.onc.1209341

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