Affiliation:
1. Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461
Abstract
ABSTRACT
Early region 3 (E3) of group C human adenoviruses (Ad) encodes several inhibitors of tumor necrosis factor alpha (TNF-α) 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-α 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-α 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-α 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.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Reference47 articles.
1. An essential role for NF-kappaB in preventing TNF-alpha-induced cell death;Beg A. A.;Science,1996
2. Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death;Boldin M. P.;Cell,1996
3. A novel protein that interacts with the death domain of Fas/APO1 contains a sequence motif related to the death domain;Boldin M. P.;J. Biol. Chem.,1995
4. Bik, a novel death-inducing protein, shares a distinct sequence motif with Bcl-2 family proteins and interacts with viral and cellular survival-promoting proteins;Boyd J. M.;Oncogene,1995
5. Epidermal growth factor receptor is down-regulated by a 10,400 mw protein encoded by the E3 region of adenovirus;Carlin C. R.;Cell,1989
Cited by
177 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献