Differential expression of tapasin and immunoproteasome subunits in adenovirus type 5- versus type 12-transformed cells.
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-alpha, and PA28-beta 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.
Vertegaal
Alfred C O
AC
Medical Genetic Centre-Department of Molecular Cell Biology, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands.
Kuiperij
H Bea
HB
Houweling
Ada
A
Verlaan
Matty
M
van der Eb
Alex J
AJ
Zantema
Alt
A
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D017920:Antiporters / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002460:Cell Line; D002472:Cell Transformation, Viral; D017077:Culture Media, Conditioned; D003546:Cysteine Endopeptidases / Q000276:immunology* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D005805:Genes, MHC Class I; D006649:Histocompatibility Antigens / Q000235:genetics / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D007668:Kidney / Q000166:cytology; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000276:immunology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009857:Oncogenes; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D021122:Protein Subunits / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D017920:Antiporters; D018797:Cell Cycle Proteins; D017077:Culture Media, Conditioned; D004268:DNA-Binding Proteins; D006649:Histocompatibility Antigens; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones; D009097:Multienzyme Complexes; D016328:NF-kappa B; D021122:Protein Subunits; D011506:Proteins; C490050:Psme1 protein, rat; C490052:Psme2 protein, rat; D050794:STAT1 Transcription Factor; C489514:Tap2 protein, rat; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; C038353:histocompatibility antigens RT, rat; C107762:tapasin; C071692:TAP2 protein, human; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C490921:Psmb10 protein, rat