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An animal model to evaluate the function and regulation of the adaptively evolving stress protein SEP53 in oesophageal bile damage responses

Cell Stress and Chaperones volume 13, pages 375–385 (2008)Cite this article

Abstract

Squamous epithelium in mammals has evolved an atypical stress response involving down-regulation of the classic HSP70 protein and induction of sets of proteins including one named SEP53. This atypical stress response might be due to the unusual environmental pressures placed on squamous tissue. In fact, SEP53 plays a role as an anti-apoptotic factor in response to DNA damage induced by deoxycholic acid stresses implicated in oesophageal reflux disease. SEP53 also has a genetic signature characteristic of an adaptively and rapidly evolving gene, and this observation has been used to imply a role for SEP53 in immunity. Physiological models of squamous tissue are required to further define the regulation and function of SEP53. We examined whether porcine squamous epithelium would be a good model to study SEP53, since this animal suffers from a bile-reflux disease in squamous oesophageal tissue. We have (1) cloned and sequenced the porcine SEP53 locus from porcine bacterial artificial chromosome genomic DNA, (2) confirmed the strikingly divergent nature of the C-terminal portion of the SEP53 gene amongst mammals, (3) discovered that a function of the conserved N-terminal domain of the gene is to maintain cytoplasmic localisation, and (4) examined SEP53 expression in normal and diseased porcine pars oesophagea. SEP53 expression in porcine tissue was relatively confined to gastric squamous epithelium, consistent with its expression in normal human squamous epithelium. Immunohistochemical staining for SEP53 protein in normal and damaged pars oesophagea demonstrated significant stabilisation of SEP53 protein in the injured tissue. These results suggest that porcine squamous epithelium would be a robust physiological model to examine the evolution and function of the SEP53 stress pathway in modulating stress-induced responses in squamous tissue.

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Acknowledgements

This work was supported in part by grants from the Cancer Research UK, the BBSRC, and the Association for International Cancer Research.

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Authors and Affiliations

  1. CRUK p53 Signal Transduction Group, University of Edinburgh, South Crewe Road, Edinburgh, EH4 2XR, UK

    Lenny Nelson & Ted Hupp

  2. Division of Genomics and Genetics, Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian, EH25 9PS, UK

    Susan Anderson, Alan L. Archibald, Zen H. Lu & C. Bruce A. Whitelaw

  3. Division of Animal Health and Welfare, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Roslin, Midlothian, EH25 9RG, UK

    Susan Rhind & Neal McIntyre

  4. SAC Veterinary Services (Edinburgh), Bush Estate, Penicuik, Midlothian, EH26 0QE, UK

    Jill Thompson

  5. Wellcome Trust Clinical Research Facility, South Crewe Road, Edinburgh, EH4 2XU, UK

    Alison Condie

  6. Institute of Evolutionary Biology, University of Edinburgh, School of Biology, Kings Buildings, EH9 3JT, Edinburgh, UK

    Tom J. Little

  7. Masaryk Memorial Cancer Institute, Brno, Czech Republic

    Rudolf Nenutil & Borek Vojtesek

Authors
  1. Lenny Nelson
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  2. Susan Anderson
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  3. Alan L. Archibald
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  4. Susan Rhind
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  6. Alison Condie
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  7. Neal McIntyre
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  8. Jill Thompson
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  10. Borek Vojtesek
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  11. C. Bruce A. Whitelaw
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  12. Tom J. Little
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  13. Ted Hupp
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Correspondence to Ted Hupp.

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Nelson, L., Anderson, S., Archibald, A.L. et al. An animal model to evaluate the function and regulation of the adaptively evolving stress protein SEP53 in oesophageal bile damage responses. Cell Stress and Chaperones 13, 375–385 (2008). https://doi.org/10.1007/s12192-008-0037-1

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  • DOI: https://doi.org/10.1007/s12192-008-0037-1

Keywords

  • SEP53
  • p53
  • C1orf10
  • Deoxycholic acid
  • Oesophagus
  • Animal models
  • Cancer