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

Proc Natl Acad Sci U S A. 1999 Feb 2;96(3):1042-7. doi: 10.1073/pnas.96.3.1042.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics
  • Adenovirus E3 Proteins / genetics
  • Adenovirus E3 Proteins / metabolism
  • Amino Acid Sequence
  • Apoptosis
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line
  • Cell Survival / drug effects
  • Glutathione Transferase
  • Humans
  • I-kappa B Kinase
  • Leucine Zippers
  • Molecular Sequence Data
  • Molecular Weight
  • NF-kappa B / metabolism*
  • NF-kappaB-Inducing Kinase
  • Protein Kinases / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Proteins / metabolism
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Transcriptional Activation / drug effects
  • Tumor Necrosis Factor-alpha / pharmacology
  • Tumor Necrosis Factor-alpha / physiology*
  • Zinc Fingers

Substances

  • Adenovirus E3 Proteins
  • Carrier Proteins
  • NF-kappa B
  • Proteins
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Glutathione Transferase
  • Protein Kinases
  • Protein Serine-Threonine Kinases
  • RIPK1 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • CHUK protein, human
  • I-kappa B Kinase
  • IKBKB protein, human
  • IKBKE protein, human

Associated data

  • GENBANK/AF062089