Differential expression of tapasin and immunoproteasome subunits in adenovirus type 5- versus type 12-transformed cells

J Biol Chem. 2003 Jan 3;278(1):139-46. doi: 10.1074/jbc.M206267200. Epub 2002 Oct 28.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 3
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Adenoviridae / genetics*
  • Adenoviridae / metabolism
  • Animals
  • Animals, Newborn
  • Antiporters / genetics
  • Antiporters / metabolism*
  • Cell Cycle Proteins
  • Cell Line
  • Cell Transformation, Viral*
  • Culture Media, Conditioned
  • Cysteine Endopeptidases / immunology*
  • Cysteine Endopeptidases / metabolism
  • DNA-Binding Proteins / metabolism
  • Flow Cytometry
  • Gene Expression Regulation*
  • Genes, MHC Class I
  • Histocompatibility Antigens / genetics
  • Histocompatibility Antigens / metabolism
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism*
  • Immunoglobulins / genetics
  • Immunoglobulins / metabolism*
  • Interferon-gamma / metabolism
  • Kidney / cytology
  • Membrane Transport Proteins
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Multienzyme Complexes / immunology*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Oncogenes
  • Phosphorylation
  • Proteasome Endopeptidase Complex
  • Protein Subunits / metabolism
  • Proteins / metabolism
  • Rats
  • STAT1 Transcription Factor
  • Trans-Activators / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 3
  • ATP-Binding Cassette Transporters
  • Antiporters
  • Cell Cycle Proteins
  • Culture Media, Conditioned
  • DNA-Binding Proteins
  • Histocompatibility Antigens
  • Histocompatibility Antigens Class I
  • Immunoglobulins
  • Membrane Transport Proteins
  • Molecular Chaperones
  • Multienzyme Complexes
  • NF-kappa B
  • Protein Subunits
  • Proteins
  • Psme1 protein, rat
  • Psme2 protein, rat
  • STAT1 Transcription Factor
  • Tap2 protein, rat
  • Trans-Activators
  • Tumor Necrosis Factor-alpha
  • histocompatibility antigens RT, rat
  • tapasin
  • TAP2 protein, human
  • Interferon-gamma
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • Psmb10 protein, rat