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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

Lookup NU author(s): Dr Jared Thornton, Caroline Dalgliesh, Dr Julian Venables, Dr Ingrid Ehrmann, Professor David Elliott

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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. © 2006 Nature Publishing Group All rights reserved.


Publication metadata

Author(s): Thornton JK, Dalgleish C, Venables JP, Sergeant KA, Ehrmann IE, Lu X, Saunders PTK, Elliott DJ

Publication type: Article

Publication status: Published

Journal: Oncogene

Year: 2006

Volume: 25

Issue: 22

Pages: 3104-3112

ISSN (print): 0950-9232

ISSN (electronic): 1476-5594

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/sj.onc.1209341

DOI: 10.1038/sj.onc.1209341

PubMed id: 16474851


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