Roles of the stress-induced gene IEX-1 in regulation of cell death and oncogenesis

Apoptosis. 2003 Jan;8(1):11-8. doi: 10.1023/a:1021688600370.

Abstract

In response to changes in the external environment cells must initiate a coordinated program of gene expression for them to adapt. IEX-1 (immediate early response gene X-1) is precisely regulated by multiple transcription factors among which p53, NF-kappaB/rel, Sp1 and c-Myc play central roles, to ensure rapid and transient expression of IEX-1 in cells under a variety of stress conditions. Overexpression of IEX-1 renders some cells sensitive to apoptosis and accelerates cell cycle progression, but reduces proliferation of other cells, whereas disruption of IEX-1 expression is associated with decreases in both apoptosis and cell cycle progression. In sharp contrast to in vitro studies, in vivo constitutive expression of IEX-1 prevents activated T cells but not B cells from apoptosis, as shown using IEX-1-transgenic mice that target IEX-1 expression specifically to lymphocytes driven by the Emu enhancer. The animals developed a lupus-like disease and subsequently a high incidence of T cell lymphomas when they aged, due to insufficient apoptosis of T cells. These varied effects of IEX-1 on cell death and cell cycle progression in a cell-context dependent fashion implicate that IEX-1 is involved in more than one signaling pathway, understanding of which will certainly improve our knowledge with respect to cancer biology, cell death and cell cycle regulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Cell Cycle
  • Cell Death
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immediate-Early Proteins / metabolism*
  • Immediate-Early Proteins / physiology*
  • Membrane Proteins
  • Mice
  • Models, Biological
  • Models, Genetic
  • NF-kappa B / metabolism
  • Neoplasm Proteins / metabolism*
  • Neoplasm Proteins / physiology*
  • Neoplasms / metabolism*
  • Transcription, Genetic
  • Tumor Suppressor Protein p53 / physiology

Substances

  • Apoptosis Regulatory Proteins
  • IER3 protein, human
  • Immediate-Early Proteins
  • Membrane Proteins
  • NF-kappa B
  • Neoplasm Proteins
  • Tumor Suppressor Protein p53