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Identification of a cell protein (FIP-3) as a modulator of NF-kappaB activity and as a target of an adenovirus inhibitor of tumor necrosis factor alpha-induced apoptosis.

FIP-3 (14.7K interacting protein) was discovered during a search for cell proteins that could interact with an adenovirus protein (Ad E3-14.7K) that had been shown to prevent tumor necrosis factor (TNF)-alpha-induced cytolysis. FIP-3, which contains leucine zippers and a zinc finger domain, inhibits both basal and induced transcriptional activity of NF-kappaB and causes a late-appearing apoptosis with unique morphologic manifestations. Ad E3-14.7K can partially reverse apoptotic death induced by FIP-3. FIP-3 also was shown to bind to other cell proteins, RIP and NIK, which previously had been described as essential components of TNF-alpha-induced NF-kappaB activation. In addition, FIP-3 inhibited activation of NF-kappaB induced by TNF-alpha, the TNFR-1 receptor, RIP, NIK, and IKKbeta, as well as basal levels of endogenous NF-kappaB in 293 cells. Because the activation of NF-kappaB has been shown to inhibit apoptosis, FIP-3 appears both to activate a cell-death pathway and to inhibit an NF-kappaB-dependent survival mechanism.

Pubmed ID: 9927690 RIS Download

Mesh terms: Adenoviridae | Adenovirus E3 Proteins | Amino Acid Sequence | Apoptosis | Carrier Proteins | Cell Line | Cell Survival | Glutathione Transferase | Humans | I-kappa B Kinase | Leucine Zippers | Molecular Sequence Data | Molecular Weight | NF-kappa B | Protein Kinases | Protein-Serine-Threonine Kinases | Proteins | Receptor-Interacting Protein Serine-Threonine Kinases | Recombinant Fusion Proteins | Recombinant Proteins | Sequence Alignment | Sequence Homology, Amino Acid | Transcriptional Activation | Tumor Necrosis Factor-alpha | Zinc Fingers

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Associated grants

  • Agency: NIAID NIH HHS, Id: T32 AI007506
  • Agency: NCI NIH HHS, Id: T32 CA009060
  • Agency: NCI NIH HHS, Id: CA13330
  • Agency: NCI NIH HHS, Id: 5T32CA 09060
  • Agency: NCI NIH HHS, Id: R01 CA72963
  • Agency: NCI NIH HHS, Id: P30 CA013330

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