Synthesis and turnover of beta2-microglobulin in Ad12-transformed cells defective in assembly and transport of class I major histocompatibility complex molecules.
In primary embryonal fibroblasts from transgenic mice expressing H-2 genes and a miniature swine class I transgene (PD1), transformation with the highly oncogenic Ad12 results in a reduction in peptide transporter and proteasome-associated (LMP2 and LMP7) gene expression, and suppression in transport and cell surface expression of all class I antigens. The selective suppression in transport of H-2 (but not of PD1) molecules in cells reconstituted for the expression of peptide transporter and LMP genes implied that an additional factor(s) is involved in the assembly of class I complexes. Here we show that the beta2m, H-2Db, and H-2Kb genes are transcribed and translated in Ad12-transformed cells. However, unlike normal and E1Ad5-transformed cells, in which beta2m is either secreted unbound or bound to class I heavy chains, in Ad12-transformed cells significant amounts of beta2m are retained in the cell bound to the membrane, but free of class I heavy chains. This abnormal turnover of beta2m in the Ad12-transformed cells suggests the existence of a novel beta2m-binding molecule(s) that sequesters beta2m, and this process may provide a mechanism by which transformation with Ad12 may subvert class I complex formation.
Mey-Tal
S V
SV
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Israel.
Schechter
C
C
Ehrlich
R
R
D000260:Adenoviruses, Human; D000818:Animals; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000378:metabolism; D002472:Cell Transformation, Viral; D003546:Cysteine Endopeptidases; D005805:Genes, MHC Class I; D006183:H-2 Antigens / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009097:Multienzyme Complexes; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D013045:Species Specificity; D013552:Swine; D014158:Transcription, Genetic; D014763:Viral Matrix Proteins / Q000378:metabolism*; D001613:beta 2-Microglobulin / Q000235:genetics*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D046911:Macromolecular Substances; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D011506:Proteins; D012333:RNA, Messenger; D014763:Viral Matrix Proteins; D001613:beta 2-Microglobulin; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex