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 NF kap pa B-mediated survival in Jurkat cells [Wu et al. (1998) Science 281, 998-1 001], 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(PRG/IEX-1). Direct DNA sequencing of PCR products g enerated 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 an d 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 amo unts of nonmutated nonspliced p22(IEX-1/PRG1) pre-mRNA were identified in t he nucleus, Thus, IEX-1L seems to be a mutant variant of p22(IEX-1/PRG1) no t existing in vivo. Antiapoptotic effects obviously represent transdominant negative inhibition of endogenous p22(PRG1/IEX-1) in Jurkat cells and seve ral other tumor cell lines. (C) 1999 Academic Press.