The putative apoptosis inhibitor IEX-1L is a mutant nonspliced variant of p22(PRG1/IEX-1) and is not expressed in vivo

Biochem Biophys Res Commun. 1999 Aug 19;262(1):139-45. doi: 10.1006/bbrc.1999.1131.

Abstract

IEX-1L has been claimed to act as an apoptosis inhibitor involved in NFkappaB-mediated survival in Jurkat cells [Wu et al. (1998) Science 281, 998-1001]. It represents a mutant nonspliced variant of the early response gene p22(PRG1/IEX-1) exhibiting one insertion and two deletions compared to the genomic sequence of p22(PRG1/IEX-1). Direct DNA sequencing of PCR products generated from human genomic DNA only detected the regular genomic sequence of p22(PRG1/IEX-1). No IEX-1L mRNA could be identified by RT-PCR analysis and subsequent DNA sequencing of total, nuclear, or cytoplasmic RNA fractions from PMA-stimulated Jurkat cells. The only functional transcript residing in the cytoplasm is regularly spliced p22(IEX-1/PRG1) mRNA. Substantial amounts of nonmutated nonspliced p22(IEX-1/PRG1) pre-mRNA were identified in the nucleus. Thus, IEX-1L seems to be a mutant variant of p22(IEX-1/PRG1) not existing in vivo. Antiapoptotic effects obviously represent transdominant negative inhibition of endogenous p22(PRG1/IEX-1) in Jurkat cells and several other tumor cell lines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / drug effects
  • Alternative Splicing / genetics*
  • Animals
  • Apoptosis Regulatory Proteins
  • Apoptosis*
  • Base Sequence
  • Cell Line
  • Cell Nucleus / drug effects
  • Cell Nucleus / genetics
  • Cell Survival
  • Cricetinae
  • Cytoplasm / drug effects
  • Cytoplasm / genetics
  • Gene Expression* / drug effects
  • Humans
  • Immediate-Early Proteins / chemistry
  • Immediate-Early Proteins / genetics*
  • Immediate-Early Proteins / metabolism*
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism*
  • Membrane Proteins
  • Molecular Sequence Data
  • Mutation*
  • NF-kappa B / metabolism
  • Neoplasm Proteins*
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transfection
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Apoptosis Regulatory Proteins
  • IER3 protein, human
  • Immediate-Early Proteins
  • Membrane Glycoproteins
  • Membrane Proteins
  • NF-kappa B
  • Neoplasm Proteins
  • Protein Isoforms
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Tetradecanoylphorbol Acetate