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J. Biol. Chem., Vol. 278, Issue 1, 139-146, January 3, 2003

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Differential Expression of Tapasin and Immunoproteasome Subunits in Adenovirus Type 5- Versus Type 12-transformed Cells^*

Alfred C. O. Vertegaal, H. Bea Kuiperij, Ada Houweling, Matty Verlaan, Alex J. van der Eb, and Alt Zantema^§

From the Medical Genetic Centre-Department of Molecular Cell Biology, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands

Adenovirus type 12 (Ad12)-transformed baby rat kidney (BRK) cells are oncogenic in syngeneic immunocompetent rats in contrast to adenovirus type 5 (Ad5)-transformed BRK cells, which are not oncogenic in these animals. A significant factor contributing to the difference in oncogenicity may be the low levels of major histocompatibility complex (MHC) class I membrane expression in Ad12-transformed BRK cells as compared with those in Ad5-transformed BRK cells, which presumably results in escape from killing by cytotoxic T lymphocytes. Here we show that, in addition to the decreased levels of expression of the MHC class I heavy chain and the peptide transporter Tap-2, the expression levels of the chaperone Tapasin and the immunoproteasome components MECL-1, PA28-, and PA28- also are much lower in Ad12- than in Ad5-transformed BRK cells. The low expression levels of these proteins may contribute to the escape from killing by cytotoxic T lymphocytes, because the generation of optimal peptides and loading of these peptides on MHC class I require these components. Increased levels of phosphorylated signal transducer and activator of transcription-1 protein and expression of IFN regulatory factor-7 were found in Ad5- versus Ad12-transformed BRK cells. Therefore, the critical alteration leading to the plethora of differences may be an interferon (-related) effect.

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