Pim kinases are upregulated during Epstein-Barr virus infection and enhance EBNA2 activity.
Latent Epstein-Barr virus (EBV) infection is strongly associated with B-cell proliferative diseases such as Burkitt's lymphoma. Here we show that the oncogenic serine/threonine kinases Pim-1 and Pim-2 enhance the activity of the viral transcriptional activator EBNA2. During EBV infection of primary B-lymphocytes, the mRNA expression levels of pim genes, especially of pim-2, are upregulated and remain elevated in latently infected B-cell lines. Thus, EBV-induced upregulation of Pim kinases and Pim-stimulated EBNA2 transcriptional activity may contribute to the ability of EBV to immortalize B-cells and predispose them to malignant growth.
Rainio
Eeva-Marja
EM
Turku Centre for Biotechnology, University of Turku/Abo Akademi University, Tykistökatu 6B, 20520 Turku, Finland.
Ahlfors
Helena
H
Carter
Kara L
KL
Ruuska
Marja
M
Matikainen
Sampsa
S
Kieff
Elliott
E
Koskinen
Päivi J
PJ
D001402:B-Lymphocytes / Q000201:enzymology / Q000821:virology; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000235:genetics; D004720:Endonucleases; D020031:Epstein-Barr Virus Infections / Q000201:enzymology* / Q000209:etiology / Q000235:genetics* / Q000821:virology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051573:Proto-Oncogene Proteins c-pim-1; D015533:Transcriptional Activation; D015854:Up-Regulation; D014764:Viral Proteins
C402641:EBNA-2 protein, Human herpesvirus 4; D019309:Epstein-Barr Virus Nuclear Antigens; D009687:Nuclear Proteins; C490587:PIM2 protein, human; D011518:Proto-Oncogene Proteins; D014764:Viral Proteins; D004247:DNA; C496634:PIM1 protein, human; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1; D004720:Endonucleases; C095221:SND1 protein, human