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The p36 isoform of BAG-1 is translated by internal ribosome entry following heat shock

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Abstract

BAG-1 (also known as RAP46/HAP46) was originally identified as a 46 kDa protein that bound to and enhanced the anti-apoptotic properties of Bcl-2. BAG-1 exists as three major isoforms (designated p50, p46 and p36 or BAG-1L, BAG-1M and BAG-1S respectively) and one minor isoform (p29), which are translated from a common transcript. The differing amino terminus determines both the intracellular location and the repertoire of binding partners of the isoforms which play different roles in a variety of cellular processes including signal transduction, heat shock, apoptosis and transcription. Although in vitro data suggest that the four BAG-1 isoforms are translated by leaky scanning, the patterns of isoform expression in vivo, especially in transformed cells, do not support this hypothesis. We have performed in vivo analysis of the BAG-1 5′ untranslated region and shown that translation initiation of the most highly expressed isoform (p36/BAG-1S) can occur by both internal ribosome entry and cap-dependent scanning. Following heat shock, when there is a downregulation of cap-dependent translation, the expression of the p36 isoform of BAG-1 is maintained by internal ribosome entry.

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Acknowledgements

This research was supported by grants from the BBSRC (advanced research fellowship to AE Willis), the LRF (ML de Schoolmeester) and the AICR (grant held by G Packham). MJ Coldwell and BM Pickering hold MRC studentships. We thank Fiona Wilson for some of the early cell line work.

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Author notes

  1. Mark J Coldwell

    Present address: School of Biological Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, UK

  2. Matthew L deSchoolmeester

    Present address: Department of Immunology, School of Biological Sciences, University of Manchester, Manchester, M13 9PT, UK

Authors and Affiliations

  1. Department of Biochemistry, University of Leicester, University Road, Leicester, LE1 7RH, UK

    Mark J Coldwell, Matthew L deSchoolmeester, Graham A Fraser, Becky M Pickering & Anne E Willis

  2. Oncology Unit, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK

    Graham Packham

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  1. Mark J Coldwell
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  2. Matthew L deSchoolmeester
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  3. Graham A Fraser
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  4. Becky M Pickering
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  5. Graham Packham
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  6. Anne E Willis
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Correspondence to Anne E Willis.

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Coldwell, M., deSchoolmeester, M., Fraser, G. et al. The p36 isoform of BAG-1 is translated by internal ribosome entry following heat shock. Oncogene 20, 4095–4100 (2001). https://doi.org/10.1038/sj.onc.1204547

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