Systematic name M15412
Brief description Genes up-regulated in Hc cells (normal hepatocyte) by TNF [GeneID=7124].
Full description or abstract Using a cDNA microarray analysis, we identified x-ray-inducible immediate early response factor-1 (IEX-1) as a proapoptotic gene which was induced by TNF-alpha and also depend on NF-kappaB activation in Hc human hepatocytes. In these cells only the original form of IEX-1, termed IEX-1S, but not its longer transcript IEX-1L, was expressed. Overexpression of IEX-1S resulted in promotion of TNF-alpha-induced apoptosis in Hc cells expressing a mutant form of IkappaB. This proapoptotic action can be explained by its inhibitory findings on survival signals; inhibition of TNF-alpha-induced activation and expression of phosphatidylinositol 3-kinase (PI3K)/Akt, and also blockage of expression of Mcl-1, an antiapoptotic Bcl-2 family member which is located downstream of Akt, was inhibited by IEX-1S. LY 294002, an inhibitor of PI3K, increased IEX-1S expression induced by TNF-alpha and accelerated TNF-alpha-induced apoptosis in IkappaB-treated Hc cells. Overexpression of the dominant-negative Akt enhanced, but the constitutively active Akt suppressed, TNF-alpha-induced IEX-1S expression, suggesting that PI3K/Akt negatively regulated IEX-1S expression. These results demonstrate that NF-kappaB-dependent recruitment of IEX-1S may play a proapoptotic role in TNF-alpha-stimulated hepatocytes through blockage of the PI3K/Akt pathway. Moreover, the reciprocal cross-talk between IEX-1S and PI3K/Akt may closely be involved in the regulation of TNF-alpha-induced hepatocyte apoptosis.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 12682234   Authors: Osawa Y,Nagaki M,Banno Y,Brenner DA,Nozawa Y,Moriwaki H,Nakashima S
Exact source Table 1
Related gene sets (show 2 gene sets from the same authors)
External links
Filtered by similarity ?
Source species Homo sapiens
Contributed by Yujin Hoshida (Broad Institute)
Source platform or
identifier namespace
Dataset references  
Download gene set format: grp | gmt | xml | json | TSV metadata
Compute overlaps ? (show collections to investigate for overlap with this gene set)
Compendia expression profiles ? NG-CHM interactive heatmaps
(Please note that clustering takes a few seconds)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)

Legacy heatmaps (PNG)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 10 genes
Gene families ? Categorize these 10 genes by gene family
Show members (show 15 source identifiers mapped to 10 genes)
Version history 3.0: Renamed from OSAWA_TNFA_HEPATOCYTE_UP

See MSigDB license terms here. Please note that certain gene sets have special access terms.