Human Gene Set: ZHOU_TNF_SIGNALING_4HR


Standard name ZHOU_TNF_SIGNALING_4HR
Systematic name M1520
Brief description Genes up-regulated in HeLa cells (cervical carcinoma) at 4 h after stimulation with TNF [GeneID=7124].
Full description or abstract Tumor necrosis factor alpha (TNF alpha) is a proinflammatory cytokine with important roles in regulating inflammatory responses as well as cell cycle proliferation and apoptosis. Although TNFalpha stimulates apoptosis, it also activates the transcription factor NF-kappa B, and studies have shown that inhibition of NF-kappa B potentiates the cytotoxicity of TNFalpha. Since several chemotherapy agents act like TNFalpha to both promote apoptosis and activate NF-kappa B, understanding the role of NF-kappa B in suppressing apoptosis may have significant clinical applications. To understand the effects of stimulation with TNFalpha and the role of NF-kappa B in regulating this response, a 23k human cDNA microarray was used to screen TNFalpha-inducible genes in HeLa cells. Real-time PCR verified expression changes in 16 of these genes and revealed three distinct temporal patterns of expression after TNFalpha stimulation. Using RNA interference to disrupt expression of the p65 subunit of NF-kappa B, all but two of the genes were shown to depend on this transcription factor for their expression, which correlated well with the existence of NF-kappa B binding sites in most of their promoters. Inflammatory, proapoptotic, and antiapoptotic genes were all shown to be regulated by NF-kappa B, demonstrating the wide variety of targets activated by NF-kappa B signaling and the necessity of differentiating among these genes for therapeutic purposes.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 12673210   Authors: Zhou A,Scoggin S,Gaynor RB,Williams NS
Exact source Table 2
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Source species Homo sapiens
Contributed by John Newman (University of Washington)
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HUMAN_SEQ_ACCESSION
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Version history 3.1: First introduced

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