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
Molecular and cellular biology
March 19, 1998
- Agency: NCI NIH HHS, Id: 5T32 CA 09060
- Agency: NCI NIH HHS, Id: P30-CA13330
- Agency: NCI NIH HHS, Id: R01-CA72963
- Adenovirus E3 Proteins
- Amino Acid Sequence
- Antigens, CD
- Base Sequence
- Carrier Proteins
- Cell Line
- DNA, Complementary
- Gene Expression
- HeLa Cells
- Leucine Zippers
- 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
- Glaucoma, normal tension, susceptibility to is related to genes OPTN, GLC1E, FIP2, HYPL, NRP, ALS12.
- Glaucoma 1, open angle, E is related to genes OPTN, GLC1E, FIP2, HYPL, NRP, ALS12 which are autosomal dominant according to the OMIM database.
- Amyotrophic lateral sclerosis 12 is related to genes OPTN, GLC1E, FIP2, HYPL, NRP, ALS12.