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Regulation of BAG-1 IRES-mediated translation following chemotoxic stress

Oncogene volume 27, pages 1167–1174 (2008)Cite this article

Abstract

There are three major isoforms of BAG-1 in mammalian cells, termed BAG-1L (p50), BAG-1M (p46) and BAG-1S (p36) that function as pro-survival proteins and are associated with tumorigenesis and chemoresistance. Initiation of BAG-1 protein synthesis can occur by both cap-dependent and cap-independent mechanisms and it has been shown that synthesis of BAG-1S is dependent upon the presence of an internal ribosome entry segment (IRES) in the 5′-UTR of BAG-1 mRNA. We have shown previously that BAG-1 IRES–meditated initiation of translation requires two trans-acting factors poly (rC) binding protein 1 (PCBP1) and polypyrimidine tract binding protein (PTB) for function. The former protein allows BAG-1 IRES RNA to attain a structure that permits binding of the ribosome, while the latter protein appears to be involved in ribosome recruitment. Here, we show that the BAG-1 IRES maintains synthesis of BAG-1 protein following exposure of cells to the chemotoxic drug vincristine but not to cisplatin and that this is brought about, in part, by the relocalization of PTB and PCBP1 from the nucleus to the cytoplasm.

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Acknowledgements

This work was supported by grants from the BBSRC (HCD; KAS; TH; MB, David Phillips fellowship) and the LRF (KH).

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Author notes

  1. M J Coldwell

    Present address: 3Current address: School of Life Sciences, University of Sussex, Falmer, Brighton, BN9, UK.,

  2. H C Dobbyn and K Hill: These authors contributed equally to this work.

Authors and Affiliations

  1. School of Pharmacy, University of Nottingham, Nottingham, UK

    H C Dobbyn, K Hill, T L Hamilton, K A Spriggs, B M Pickering, M J Coldwell, C H de Moor, M Bushell & A E Willis

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  1. H C Dobbyn
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  2. K Hill
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  3. T L Hamilton
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  4. K A Spriggs
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  7. C H de Moor
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  9. A E Willis
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Correspondence to A E Willis.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Dobbyn, H., Hill, K., Hamilton, T. et al. Regulation of BAG-1 IRES-mediated translation following chemotoxic stress. Oncogene 27, 1167–1174 (2008). https://doi.org/10.1038/sj.onc.1210723

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