Unr, a cytoplasmic rna-binding protein with cold-shock domains, is involved in control of apoptosis in es and huh7 cells

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 Gadd45_γ_,

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

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Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS THE LINCRNA _JUNI_ REGULATES THE STRESS-DEPENDENT INDUCTION OF C-JUN, CELLULAR MIGRATION AND SURVIVAL THROUGH THE MODULATION

OF THE DUSP14-JNK AXIS Article Open access 02 April 2024 PUMA FACILITATES EMI1-PROMOTED CYTOPLASMIC RAD51 UBIQUITINATION AND INHIBITS DNA REPAIR IN STEM AND PROGENITOR CELLS Article Open

access 31 March 2021 SHQ1 IS AN ER STRESS RESPONSE GENE THAT FACILITATES CHEMOTHERAPEUTICS-INDUCED APOPTOSIS VIA SENSITIZING ER-STRESS RESPONSE Article Open access 10 June 2020 ACCESSION

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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. AUTHOR INFORMATION

Author notes * V Dormoy-Raclet and J Markovits: These authors contributed equally to this work. AUTHORS AND AFFILIATIONS * INSERM, E362, Bordeaux, France V Dormoy-Raclet, J Markovits, Y

Malato, A Jacquemin-Sablon & H Jacquemin-Sablon * Université Victor Segalen Bordeaux 2, Bordeaux, France V Dormoy-Raclet, J Markovits, Y Malato, A Jacquemin-Sablon & H

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Correspondence to H Jacquemin-Sablon. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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

Download citation * Received: 04 February 2005 * Revised: 28 July 2006 * Accepted: 08 September 2006 * Published: 06 November 2006 * Issue Date: 19 April 2007 * DOI:

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currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * Unr * RNA-binding protein * ES and HuH7 cells *

_γ_-irradiation * apoptosis * proliferation