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Journal of Virology, April 2002, p. 3212-3220, Vol. 76, No. 7
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.7.3212-3220.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

In Adenovirus Type 12 Tumorigenic Cells, Major Histocompatibility Complex Class I Transcription Shutoff Is Overcome by Induction of NF-{kappa}B and Relief of COUP-TFII Repression

Shihe Hou,1,2 Hancheng Guan,1 and Robert P. Ricciardi1,2*

Department of Microbiology, School of Dental Medicine,1 Department of Biochemistry and Molecular Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 191042

Received 14 September 2001/ Accepted 29 December 2001

The surface levels of major histocompatibility complex class I antigens are diminished on tumorigenic adenovirus type 12 (Ad12)-transformed cells, enabling them to escape from immunosurveillant cytotoxic T lymphocytes (CTLs). This is due to the down-regulation of the class I transcriptional enhancer, in which there is strong binding of the repressor COUP-TFII and lack of binding of the activator NF-{kappa}B. Even though NF-{kappa}B (p65/p50) translocates to the nuclei of Ad12-transformed cells, it fails to bind to DNA efficiently due to the hypophosphorylation of the p50 subunit. In this study, tumor necrosis factor alpha (TNF-{alpha}) and interleukin 1ß (IL-1ß) were shown to promote degradation of the NF-{kappa}B cytoplasmic inhibitor I{kappa}B{alpha} and permit the nuclear translocation of a phosphorylated form of NF-{kappa}B that is capable of binding DNA. Interestingly, when Ad12-transformed cells were treated with TNF-{alpha} or IL-1ß, class I gene transcription substantially increased when transcriptional repression by COUP-TFII was blocked. This indicates that in cytokine-treated Ad12-transformed cells, COUP-TFII is able to repress activation of class I transcription by newly nucleus-localized NF-{kappa}B. Our results suggest that Ad12 likely employs a "fail-safe" mechanism to ensure that the transcription of class I genes remains tightly repressed under various physiological conditions, thus providing tumorigenic Ad12-transformed cells with a means of escaping CTL recognition and lysis.

* Corresponding author. Mailing address: University of Pennsylvania, Levy Research Building, Room 221, 4010 Locust St., Philadelphia, PA 19104. Phone: (215) 898-3905. Fax: (215) 898-8385. E-mail: ricciardi{at}biochem.dental.upenn.edu.

Journal of Virology, April 2002, p. 3212-3220, Vol. 76, No. 7
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.7.3212-3220.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Guan, H., Jiao, J., Ricciardi, R. P. (2008). Tumorigenic Adenovirus Type 12 E1A Inhibits Phosphorylation of NF-{kappa}B by PKAc, Causing Loss of DNA Binding and Transactivation. J. Virol. 82: 40-48 [Abstract] [Full Text]  
  • Guan, H., Hou, S., Ricciardi, R. P. (2005). DNA Binding of Repressor Nuclear Factor-{kappa}B p50/p50 Depends on Phosphorylation of Ser337 by the Protein Kinase A Catalytic Subunit. J. Biol. Chem. 280: 9957-9962 [Abstract] [Full Text]  
  • Kurtev, V., Margueron, R., Kroboth, K., Ogris, E., Cavailles, V., Seiser, C. (2004). Transcriptional Regulation by the Repressor of Estrogen Receptor Activity via Recruitment of Histone Deacetylases. J. Biol. Chem. 279: 24834-24843 [Abstract] [Full Text]  
  • Hou, S., Guan, H., Ricciardi, R. P. (2003). Phosphorylation of Serine 337 of NF-{kappa}B p50 Is Critical for DNA Binding. J. Biol. Chem. 278: 45994-45998 [Abstract] [Full Text]  
  • Petersen, J. L., Morris, C. R., Solheim, J. C. (2003). Virus Evasion of MHC Class I Molecule Presentation. J. Immunol. 171: 4473-4478 [Full Text]  


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