Immediate Early Response 3 (IER3)

IER3 had an in-frame insertion of 111 nucleotides at position 211 of the coding region of IEX1, and could encode a longer polypeptide with a 37-amino acid insertion relative to IEX1. The longer IEX1 (referred to as IEX1L; the original IEX1 was referred to as IEX1S) was found to be generated from IEX1 in the absence of RNA splicing as it contained the entire intron sequence of IEX1. The transcription of IEX1L induced by TNF was decreased in cells with defective NF-kappa-B activation, rendering them sensitive to TNF-induced apoptosis, which was abolished by transfection with IEX1L. In support, overexpression of antisense IEX1L partially blocked TNF-induced expression of IEX1L and sensitized normal cells to killing. This study demonstrated a key role of IEX1L in cellular resistance to TNF-induced apoptosis.