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

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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.