IEX-1L, an Apoptosis Inhibitor Involved in NF-κB-Mediated Cell Survival

Transcription factors of the nuclear factor–κB/rel (NF-κB) family may be important in cell survival by regulating unidentified, anti-apoptotic genes. One such gene that protects cells from apoptosis induced by Fas or tumor necrosis factor type α (TNF), IEX- 1L, is described here. Its transcription induced by TNF was decreased in cells with defective NF-κB activation, rendering them sensitive to TNF-induced apoptosis, which was abolished by transfection with IEX- 1L. In support, overexpression of antisense IEX- 1L partially blocked TNF-induced expression of IEX -1L and sensitized normal cells to killing. This study demonstrates a key role of IEX- 1L in cellular resistance to TNF-induced apoptosis.

[1]  D. Wallach,et al.  Cell death induction by TNF: a matter of self control. , 1997, Trends in biochemical sciences.

[2]  S. Nagata,et al.  Apoptosis by Death Factor , 1997, Cell.

[3]  David Baltimore,et al.  An Essential Role for NF-κB in Preventing TNF-α-Induced Cell Death , 1996, Science.

[4]  D. Katz,et al.  Inhibition of NF‐kappaB/Rel induces apoptosis of murine B cells. , 1996, The EMBO journal.

[5]  S. Korsmeyer,et al.  Molecular thanatopsis: a discourse on the BCL2 family and cell death. , 1996, Blood.

[6]  U. Fölsch,et al.  PRG1: a novel early-response gene transcriptionally induced by pituitary adenylate cyclase activating polypeptide in a pancreatic carcinoma cell line. , 1996, Cancer research.

[7]  M. Jung,et al.  Identification and characterization of a radiation-inducible glycosylated human early-response gene. , 1996, Cancer research.

[8]  Hong-Bing Shu,et al.  TRADD–TRAF2 and TRADD–FADD Interactions Define Two Distinct TNF Receptor 1 Signal Transduction Pathways , 1996, Cell.

[9]  David Baltimore,et al.  Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-κB , 1995, Nature.

[10]  S. Gerstberger,et al.  Control of I kappa B-alpha proteolysis by site-specific, signal-induced phosphorylation , 1995, Science.

[11]  W. Fiers,et al.  Molecular mechanisms of tumor necrosis factor‐induced cytotoxicity , 1994, FEBS letters.

[12]  L. Lau,et al.  Genomic structure, cDNA sequence, and expression of gly96, a growth factor-inducible immediate-early gene encoding a short-lived glycosylated protein. , 1993, Oncogene.

[13]  A. Baldwin,et al.  THE NF-κB AND IκB PROTEINS: New Discoveries and Insights , 1996 .