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Interaction of an adenovirus E3 14.7-kilodalton protein with a novel tumor necrosis factor alpha-inducible cellular protein containing leucine zipper domains.

Early region 3 (E3) of group C human adenoviruses (Ad) encodes several inhibitors of tumor necrosis factor alpha (TNF-alpha) cytolysis, including an E3 14.7-kDa protein (E3-14.7K) and a heterodimer containing two polypeptides of 10.4 and 14.5 kDa. To understand the mechanism by which the viral proteins inhibit TNF-alpha functions, the E3-14.7K protein was used to screen a HeLa cell cDNA library to search for interacting proteins in the yeast two-hybrid system. A novel protein containing multiple leucine zipper domains without any significant homology with any known protein was identified and has been named FIP-2 (for 14.7K-interacting protein). FIP-2 interacted with E3-14.7K both in vitro and in vivo. It colocalized with Ad E3-14.7K in the cytoplasm, especially near the nuclear membrane, and caused redistribution of the viral protein. FIP-2 by itself does not cause cell death; however, it can reverse the protective effect of E3-14.7K on cell killing induced by overexpression of the intracellular domain of the 55-kDa TNF receptor or by RIP, a death protein involved in the TNF-alpha and Fas apoptosis pathways. Deletion analysis indicates that the reversal effect of FIP-2 depends on its interaction with E3-14.7K. Three major mRNA forms of FIP-2 have been detected in multiple human tissues, and expression of the transcripts was induced by TNF-alpha treatment in a time-dependent manner in two different cell lines. FIP-2 has consensus sequences for several potential posttranslational modifications. These data suggest that FIP-2 is one of the cellular targets for Ad E3-14.7K and that its mechanism of affecting cell death involves the TNF receptor, RIP, or a downstream molecule affected by either of these two molecules.

Pubmed ID: 9488477


  • Li Y
  • Kang J
  • Horwitz MS


Molecular and cellular biology

Publication Data

March 19, 1998

Associated Grants

  • Agency: NCI NIH HHS, Id: 5T32 CA 09060
  • Agency: NCI NIH HHS, Id: P30-CA13330
  • Agency: NCI NIH HHS, Id: R01-CA72963

Mesh Terms

  • Adenovirus E3 Proteins
  • Amino Acid Sequence
  • Animals
  • Antigens, CD
  • Base Sequence
  • Carrier Proteins
  • Cell Line
  • DNA, Complementary
  • Gene Expression
  • HeLa Cells
  • Humans
  • Leucine Zippers
  • Mice
  • Molecular Sequence Data
  • Nucleic Acid Hybridization
  • RNA, Messenger
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Saccharomyces cerevisiae
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha