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Molecular and Cellular Biology, March 1999, p. 2169-2179, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Reduced Phosphorylation of p50 Is Responsible for Diminished NF-kappa B Binding to the Major Histocompatibility Complex Class I Enhancer in Adenovirus Type 12-Transformed Cells

David B. Kushner1,2,dagger and Robert P. Ricciardi1,3,*

Department of Microbiology, School of Dental Medicine,1 Graduate Group in Cell and Molecular Biology,2 and Department of Biochemistry and Biophysics, School of Medicine,3 University of Pennsylvania, Philadelphia, Pennsylvania 19104

Received 13 July 1998/Returned for modification 24 August 1998/Accepted 18 November 1998

Reduced cell surface levels of major histocompatibility complex class I antigens enable adenovirus type 12 (Ad12)-transformed cells to escape immunosurveillance by cytotoxic T lymphocytes (CTL), contributing to their tumorigenic potential. In contrast, nontumorigenic Ad5-transformed cells harbor significant cell surface levels of class I antigens and are susceptible to CTL lysis. Ad12 E1A mediates down-regulation of class I transcription by increasing COUP-TF repressor binding and decreasing NF-kappa B activator binding to the class I enhancer. The mechanism underlying the decreased binding of nuclear NF-kappa B in Ad12-transformed cells was investigated. Electrophoretic mobility shift assay analysis of hybrid NF-kappa B dimers reconstituted from denatured and renatured p50 and p65 subunits from Ad12- and Ad5-transformed cell nuclear extracts demonstrated that p50, and not p65, is responsible for the decreased ability of NF-kappa B to bind to DNA in Ad12-transformed cells. Hypophosphorylation of p50 was found to correlate with restricted binding of NF-kappa B to DNA in Ad12-transformed cells. The importance of phosphorylation of p50 for NF-kappa B binding was further demonstrated by showing that an NF-kappa B dimer composed of p65 and alkaline phosphatase-treated p50 from Ad5-transformed cell nuclear extracts could not bind to DNA. These results suggest that phosphorylation of p50 is a key step in the nuclear regulation of NF-kappa B in adenovirus-transformed cells.

* 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.

dagger Present address: Institute for Molecular Virology, University of Wisconsin---Madison, Madison, WI 53706.

Molecular and Cellular Biology, March 1999, p. 2169-2179, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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