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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
Purchase on Springer Link
Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
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
References
Abbadie C, Kabrun N, Bouali F, Smardova J, Stehelin D, Vandenbunder B and Enrietto PJ. . 1993 Cell 75: 899–912.
Barkett M and Gilmore TD. . 1999 Oncogene 18: 6910–6924.
Chan H, Bartos DP and Owen-Schaub LB. . 1999 Mol. Cell. Biol. 19: 2098–2108.
Charles CH, Yoon JK, Simske JS and Lau LF. . 1993 Oncogene 8: 797–801.
Chen C, Edelstein LC and Gélinas C. . 2000 Mol. Cell. Biol. 20: 2687–2695.
Dudley E, Hornung F, Zheng L, Scherer D, Ballard D and Lenardo M. . 1999 Eur. J. Immunol. 29: 878–886.
Evan G and Littlewood T. . 1998 Science 281: 1317–1322.
Gibson SB, Oyer R, Spalding AC, Anderson SM and Johnson GL. . 2000 Mol. Cell. Biol. 20: 205–212.
Guttridge DC, Albanese C, Reuther JY, Pestell RG and Baldwin Jr AS. . 1999 Mol. Cell. Biol. 19: 5785–5799.
Hellerbrand C, Jobin C, Iimuro Y, Licato L, Sartor RB and Brenner DA. . 1998 Hepatology 27: 1285–1295.
Hinz M, Krappman D, Eichten A, Heder A, Scheidereit C and Strauss M. . 1999 Mol. Cell. Biol. 19: 2690–2698.
Jiang MC, Yang-Yen HF, Lin JK and Yen JY. . 1996 Oncogene 13: 609–616.
Kaltschmidt B, Kaltschmidt C, Hehner SP, Droge W and Schmitz ML. . 1999 Oncogene 18: 3213–3225.
Kaltschmidt B, Kaltschmidt C, Hofmann TG, Hehner SP, Droge W and Schmitz ML. . 2000 Eur. J. Biochem. 267: 3828–3835.
Kobayashi T, Pittelkow MR, Warner GM, Squillace KA and Kumar R. . 1998 Biochem. Biophys. Res. Commun. 251: 868–873.
Kondratyev AD, Chung KN and Jung MO. . 1996 Cancer Res. 56: 1498–1502.
Kroll M, Arenzana-Seisdedos F, Bachelerie F, Thomas D, Friguet B and Conconi M. . 1999 Chem. Biol. 6: 689–698.
Lee HH, Dadgostar H, Cheng Q, Shu J and Cheng G. . 1999 Proc. Natl. Acad. Sci. USA 96: 9136–9141.
Lin B, Williams-Skipp C, Tao Y, Schleicher MS, Cano LL, Duke RC and Scheinman RI. . 1999 Cell. Death Differ. 6: 570–582.
Liu ZG, Hsu H, Goeddel DV and Karin M. . 1996 Cell 87: 565–576.
Okamoto K and Prives C. . 1999 Oncogene 18: 4606–4615.
Pahl HL, Krauss B, Schulze-Osthoff K, Decker T, Traenckner EB, Vogt M, Myers C, Parks T, Warring P, Muhlbacher A, Czernilofsky AP and Baeuerle PA. . 1996 J. Exp. Med. 183: 1829–1840.
Pietzsch A, Buchler C and Schmitz G. . 1998 Biochem. Biophys. Res. Commun. 245: 651–657.
Qin JZ, Chaturvedi V, Denning MF, Choubey D, Diaz MO and Nickoloff BJ. . 1999 J. Biol. Chem. 274: 37957–37964.
Rayet B and Gelinas C. . 1999 Oncogene 18: 6938–6947.
Ryan KM, Ernst MK, Rice NR and Vousden KH. . 2000 Nature 404: 892–897.
Sakamuro D, Eviner V, Elliott KJ, Showe L, White E and Prendergast GC. . 1995 Oncogene 11: 2411–2418.
Schäfer H, Arlt A, Trauzold A, Huenermann-Jansen A and Schmidt WE. . 1999 Biochem. Biophys. Res. Commun. 262: 139–145.
Schäfer H, Diebel J, Arlt A, Trauzold A and Schmidt WE. . 1998b FEBS Lett. 436: 139–143.
Schäfer H, Trauzold A, Sebens T, Deppert W, Foelsch UR and Schmidt WE. . 1998a Oncogene 16: 2479–2487.
Schäfer H, Trauzold A, Siegel EG, Foelsch UR and Schmidt WE. . 1996 Cancer Res. 56: 2641–2648.
Segev DL, Ha TU, Tran TT, Kenneally M, Harkin P, Jung M, MacLaughlin DT, Donahoe PK and Maheswaran S. . 2000 J. Biol. Chem. 275: 28371–28379.
Stehlik C, de Martin R, Kumabashiri I, Schmid JA, Binder BR and Lipp J. . 1998 J. Exp. Med. 188: 211–216.
Usami I, Kubota M, Bessho R, Kataoka A, Koishi S, Watanabe K, Sawada M, Lin YW, Akiyama Y and Furusho K. . 1998 Biochem. Pharmacol. 55: 185–191.
Van Antwerp DJ, Martin SJ, Kafri T, Green DR and Verma IM. . 1996 Science 274: 787–789.
Wahl C, Liptay S, Adler G and Schmid RM. . 1998 J. Clin. Invest. 101: 1163–1174.
Wang CY, Cusack Jr JC, Liu R and Baldwin Jr AS. . 1999a Nat. Med. 5: 412–417.
Wang CY, Guttridge DC, Mayo MW and Baldwin Jr AS. . 1999b Mol. Cell. Biol. 19: 5923–5929.
Wang CY, Mayo MW and Baldwin Jr AS. . 1996 Science 274: 784–787.
Wolff B and Naumann M. . 1999 Oncogene 18: 2663–2666.
Wu MX, Ao Z, Prasad KV, Wu R and Schlossman SF. . 1998 Science 281: 998–1001.
You M, Ku PT, Hrdlickova R and Bose Jr HR. . 1997 Mol. Cell. Biol. 17: 7328–7341.
Zong WC, Edelstein LC, Chen C, Bash J and Gelinas C. . 1999 Genes Dev. 13: 382–387.
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.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1204061
Keywords
This article is cited by
-
Linking Diabetes Mellitus with Alzheimer's Disease: Bioinformatics Analysis for the Potential Pathways and Characteristic Genes
Biochemical Genetics (2022)
-
TRAIL promotes hepatocellular carcinoma apoptosis and inhibits proliferation and migration via interacting with IER3
Cancer Cell International (2021)
-
Scaffold protein FHL2 facilitates MDM2-mediated degradation of IER3 to regulate proliferation of cervical cancer cells
Oncogene (2016)
-
Molecular signature of response and potential pathways related to resistance to the HSP90 inhibitor, 17AAG, in breast cancer
BMC Medical Genomics (2010)
-
ATM-dependent expression of IEX-1 controls nuclear accumulation of Mcl-1 and the DNA damage response
Cell Death & Differentiation (2010)