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

P22(PRG1/IEX-1) is putative NF-kappaB target gene implicated in the regulat ion of cellular viability. Here, we show that in HeLa cells TNF alpha induc es expression of p22(PRG1/IEX-1) in an NF-kappaB dependent fashion. Blockad e of NF-kappaB activation by various NF-kappaB inhibitors abolished TNF alp ha -induced p22(PRG1/IEX-1) expression and increased the sensitivity to apo ptosis induced by TNF alpha, an activating Fas-antibody or the anti-cancer drug etoposide, Surprisingly, ectopic expression of p22(PRG1/IEX-1) in HeLa cells transfected with an inducible p22(PRG1/IEX-1)-expression vector augm ents the susceptibility to apoptosis initiated by death-receptor ligands or by etoposide, In addition, p22(PRG1/IEX-1) expressing HeLa cells exhibit a n accelerated progression through the cell cycle. Transfection of an antise nse hammerhead ribozyme targeted to p22(PRG1/IEX-1) reduced the speed in ce ll cycle progression and decreased the apoptotic response to death ligands. Our data demonstrate that p22(PRG1/IEX-1) is specifically induced during N F-kappaB activation, but this seems not to be related to the anti-apoptotic actions of NF-kappaB, Instead, NF-kappaB dependent recruitment of p22(PRG1 /IEX-1) might be related to a modulation in the cell cycle, and hereby, p22 (PRG1/IEX-1) accelerate cell growth on the one hand, but may trigger apopto sis on the other.