The putative apoptosis inhibitor IEX-1L is a mutant nonspliced variant of p22(PRG1/IEX-1) and is not expressed in vivo.
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.
Schäfer
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Gastrointestinal Unit, Christian-Albrechts-University of Kiel, Kiel, 24105, Germany. hshaef@1med.uni-kiel.de
Arlt
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Trauzold
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Hünermann-Jansen
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Schmidt
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D017398:Alternative Splicing / Q000187:drug effects / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival; D006224:Cricetinae; D003593:Cytoplasm / Q000187:drug effects / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D051017:Apoptosis Regulatory Proteins; C099815:IER3 protein, human; D017874:Immediate-Early Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate