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

Oncogene. 2001 Jan 4;20(1):69-76. doi: 10.1038/sj.onc.1204061.

Abstract

P22PRG1/IEX-1 is a putative NF-kappaB target gene implicated in the regulation of cellular viability. Here, we show that in HeLa cells TNFalpha induces expression of p22PRG1/IEX-1 in an NF-kappaB dependent fashion. Blockade of NF-kappaB activation by various NF-kappaB inhibitors abolished TNFalpha-induced p22PRG1/IEX-1 expression and increased the sensitivity to apoptosis induced by TNFalpha, 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-kappaB activation, but this seems not to be related to the anti-apoptotic actions of NF-kappaB. Instead, NF-kappaB 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. Oncogene (2001) 20, 69 - 76.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Apoptosis Regulatory Proteins
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Death / genetics
  • Genetic Vectors / metabolism
  • Gliotoxin / pharmacology
  • HeLa Cells / cytology*
  • HeLa Cells / drug effects
  • HeLa Cells / metabolism*
  • Humans
  • Hydrolysis
  • Immediate-Early Proteins / biosynthesis*
  • Immediate-Early Proteins / genetics*
  • Immediate-Early Proteins / metabolism
  • Immediate-Early Proteins / physiology
  • Immunosuppressive Agents / pharmacology
  • Leucine / analogs & derivatives*
  • Leucine / pharmacology
  • Leupeptins / pharmacology
  • Membrane Glycoproteins / biosynthesis*
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism
  • Membrane Glycoproteins / physiology
  • Membrane Proteins
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • NF-kappa B / physiology*
  • Neoplasm Proteins*
  • RNA, Catalytic / metabolism
  • Sulfasalazine / pharmacology
  • Tetracycline / pharmacology
  • Transfection
  • Tumor Necrosis Factor-alpha / pharmacology
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • IER3 protein, human
  • Immediate-Early Proteins
  • Immunosuppressive Agents
  • Leupeptins
  • Membrane Glycoproteins
  • Membrane Proteins
  • NF-kappa B
  • Neoplasm Proteins
  • RNA, Catalytic
  • Tumor Necrosis Factor-alpha
  • acetyl-leucinal-leucinal-normethional
  • Sulfasalazine
  • Gliotoxin
  • Tetracycline
  • Leucine
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde