The ubiquitin/proteasome system in Epstein-Barr virus latency and associated malignancies.
Epstein-Barr virus (EBV) is a human herpesvirus associated with lymphoid and epithelial malignancies. Three viral proteins, the EBV nuclear antigen 1 and the latent membrane proteins-1 and -2A, regulate viral latency by manipulating ubiquitin-dependent proteolysis. The activation of cellular oncogenes is instrumental for the progression of EBV infected cells to full malignancy. Constitutively activation of c-myc correlates with decreased proteasomal activity and upregulation of compensatory proteolytic pathways in Burkitt's lymphomas. Knowledge of these multiple strategies of interference with regulated proteolysis may provide new clues for the treatment of EBV-associated malignancies.
Dantuma
Nico P
NP
Microbiology and Tumor Biology Center, Karolinska Institutet, Box 280, S-17177 Stockholm, Sweden.
Masucci
Maria G
MG
D002051:Burkitt Lymphoma / Q000378:metabolism / Q000821:virology*; D002472:Cell Transformation, Viral / Q000235:genetics / Q000502:physiology*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism; D016259:Genes, myc / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism; D015513:Oncogene Proteins / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051562:Proto-Oncogene Proteins c-bcr; D015398:Signal Transduction / Q000502:physiology; D014452:Ubiquitins / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000378:metabolism; D017735:Virus Latency / Q000502:physiology*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D009097:Multienzyme Complexes; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D014452:Ubiquitins; D014763:Viral Matrix Proteins; D011505:Protein-Tyrosine Kinases; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C417029:EBV-encoded nuclear antigen 1