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Unr, a cytoplasmic RNA-binding protein with cold-shock domains, is involved in control of apoptosis in ES and HuH7 cells

Oncogene volume 26, pages 2595–2605 (2007)Cite this article

Abstract

Unr (upstream of N-r as) is a cytoplasmic RNA-binding protein involved in the regulation of messenger RNA stability and internal initiation of translation. We have used Unr-deficient murine embryonic stem (ES) cells to analyse Unr role in cell proliferation and response to stress. Disruption of both unr gene copies had no effect on ES cell proliferation. However, after ionizing radiation (IR), clonogenic survival of unr−/− ES cells was ∼3-fold enhanced as compared to unr+/+ cells. We further determined that IR-induced apoptosis was decreased in unr−/− ES cells, and that reintroduction of the unr gene in unr−/− cells restored normal IR-induced apoptosis. Three pro-apoptotic genes, p53, caspase-3 and Gadd45γ, were downregulated in unr−/− ES cells, indicating that Unr, as other cytoplasmic RNA-binding proteins, regulates a complex genetic program, promoting cell death after IR. In contrast, in the human hepatoma cell line HuH7, Unr knockdown using unr-specific small interfering RNAs induced apoptosis, both in untreated and γ-irradiated cells. Thus, our results establish that Unr acts as a positive or negative regulator of cell death, depending on the cell type. Manipulating the level of Unr may constitute a specific approach to sensitize cancer cells to anticancer treatments.

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Acknowledgements

We thank E Brown and R Jackson for the generous gift of the pET-UnrCSD1* plasmid and A-B Shyu for giving us the siRNAs targeting the human unr mRNA. We also thank J Rosenbaum for helpful discussions and P Costet for excellent technical help. Finally, we thank the editor and the reviewers for most helpful comments. This work was supported by the Ligue Nationale contre le Cancer.

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  1. V Dormoy-Raclet and J Markovits: These authors contributed equally to this work.

Authors and Affiliations

  1. INSERM, E362, Bordeaux, France

    V Dormoy-Raclet, J Markovits, Y Malato, A Jacquemin-Sablon & H Jacquemin-Sablon

  2. Université Victor Segalen Bordeaux 2, Bordeaux, France

    V Dormoy-Raclet, J Markovits, Y Malato, A Jacquemin-Sablon & H Jacquemin-Sablon

  3. CNRS, FRE 2618, Institut Bergonié, Bordeaux, France

    S Huet, P Lagarde & D Montaudon

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  1. V Dormoy-Raclet
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Correspondence to H Jacquemin-Sablon.

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Dormoy-Raclet, V., Markovits, J., Malato, Y. et al. Unr, a cytoplasmic RNA-binding protein with cold-shock domains, is involved in control of apoptosis in ES and HuH7 cells. Oncogene 26, 2595–2605 (2007). https://doi.org/10.1038/sj.onc.1210068

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