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Expression of the NF-κB target gene IEX-1 (p22/PRG1) does not prevent cell death but instead triggers apoptosis in Hela cells

Abstract

P22PRG1/IEX-1 is a putative NF-κB target gene implicated in the regulation of cellular viability. Here, we show that in HeLa cells TNFα induces expression of p22PRG1/IEX-1 in an NF-κB dependent fashion. Blockade of NF-κB activation by various NF-κB inhibitors abolished TNFα-induced p22PRG1/IEX-1 expression and increased the sensitivity to apoptosis induced by TNFα, an activating Fas-antibody or the anti-cancer drug etoposide. Surprisingly, ectopic expression of p22PRG1/IEX-1 in HeLa cells transfected with an inducible p22PRG1/IEX-1-expression vector augments the susceptibility to apoptosis initiated by death-receptor ligands or by etoposide. In addition, p22PRG1/IEX-1 expressing HeLa cells exhibit an accelerated progression through the cell cycle. Transfection of an antisense hammerhead ribozyme targeted to p22PRG1/IEX-1 reduced the speed in cell cycle progression and decreased the apoptotic response to death ligands. Our data demonstrate that p22PRG1/IEX-1 is specifically induced during NF-κB activation, but this seems not to be related to the anti-apoptotic actions of NF-κB. Instead, NF-κB dependent recruitment of p22PRG1/IEX-1 might be related to a modulation in the cell cycle, and hereby, p22PRG1/IEX-1 may accelerate cell growth on the one hand, but may trigger apoptosis on the other.

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Abbreviations

NF-κB:

nuclear factor-κB

TNFα:

tumor necrosis factor α

IEX-1:

X-ray inducible immediate early gene 1

PI:

propidium iodide

FCS:

fetal calf serum

EMEM:

Eagle's Minimal Essential Medium

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Acknowledgements

The authors wish to thank Maike Breitenbroich for her excellent technical work and to Guido Krupp (Department of Haematopathology, University of Kiel) for his advice on the ribozyme technique. This work was supported by a grant (SFB-415/C3) of the German Research Society (DFG). This work is part of Ph.D. theses for A Arlt and O Grobe.

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Arlt, A., Grobe, O., Sieke, A. et al. Expression of the NF-κB target gene IEX-1 (p22/PRG1) does not prevent cell death but instead triggers apoptosis in Hela cells. Oncogene 20, 69–76 (2001). https://doi.org/10.1038/sj.onc.1204061

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