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Translational upregulation of X-linked inhibitor of apoptosis (XIAP) increases resistance to radiation induced cell death

Oncogene volume 19, pages 4174–4177 (2000)Cite this article

Abstract

Inhibitory regulators of apoptosis play a critical role in the responsiveness of tumour cells to cytotoxic agents. The X-linked inhibitor of apoptosis protein (XIAP) is a member of a novel family of Inhibitor of Apoptosis (IAP) proteins. Here we show that acute low dose ionizing irradiation results in the translational upregulation of XIAP that correlates with an increased resistance to radiation in non-small cell lung carcinoma. This upregulation is mediated by an internal ribosome binding mechanism via an IRES element located within a XIAP 5′ UTR. Transient overexpression of XIAP rendered human carcinoma cells resistant to low dose γ-irradiation. By contrast, the antisense targeting of XIAP resulted in increased cell death following irradiation advocating a distinct role for XIAP in radiation resistant phenotype of human cancers.

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Acknowledgements

We thank P Liston for the gift of adenoviral vectors, C Neville for sequencing and members of our laboratories for critical discussions. This work was supported in part by grants from the Medical Research Council of Canada (MRC), the Canadian Networks of Centers of Excellence (NCE), National Cancer Institute of Canada, Cancer Research Society, the Howard Hughes Medical Institute (HHMI), and the Apoptogen Inc. M Holcik is a recipient of a MRC Postdoctoral Fellowship. RG Korneluk is a recipient of a MRC Senior Scientist Award, A Fellow of the Royal Society of Canada, and a HHMI International Research Scholar.

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Authors and Affiliations

  1. Apoptogen Inc., 401 Smyth Road, Ottawa, K1H 8L1, Ontario, Canada

    Martin Holcik & Robert G Korneluk

  2. Solange Gauthier Karsh Molecular Genetics Laboratory, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, K1H 8L1, Ontario, Canada

    Martin Holcik & Robert G Korneluk

  3. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 401 Smyth Road, Ottawa, K1H 8L1, Ontario, Canada

    Robert G Korneluk

  4. Department of Oncology, McGill University, Montreal, H3G 1A4, Quebec, Canada

    Chiaoli Yeh & Terry Chow

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Holcik, M., Yeh, C., Korneluk, R. et al. Translational upregulation of X-linked inhibitor of apoptosis (XIAP) increases resistance to radiation induced cell death. Oncogene 19, 4174–4177 (2000). https://doi.org/10.1038/sj.onc.1203765

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