Epstein-Barr Virus Immortalization of Human B-Cells Leads to Stabilization of Hypoxia-Induced Factor 1 Alpha, Congruent with the Warburg Effect
dc.creator | Darekar, S. | en |
dc.creator | Georgiou, K. | en |
dc.creator | Yurchenko, M. | en |
dc.creator | Yenamandra, S. P. | en |
dc.creator | Chachami, G. | en |
dc.creator | Simos, G. | en |
dc.creator | Klein, G. | en |
dc.creator | Kashuba, E. | en |
dc.date.accessioned | 2015-11-23T10:25:13Z | |
dc.date.available | 2015-11-23T10:25:13Z | |
dc.date.issued | 2012 | |
dc.identifier | 10.1371/journal.pone.0042072 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/11615/26936 | |
dc.description.abstract | Background: Epstein-Barr virus (EBV) encodes six nuclear transformation-associated proteins that induce extensive changes in cellular gene expression and signaling and induce B-cell transformation. The role of HIF1A in EBV-induced B-cell immortalization has not been previously studied. Methods and Findings: Using Western blotting and Q-PCR, we found that HIF1A protein is stabilized in EBV-transformed lymphoblastoid cells. Western blotting, GST pulldown assays, and immunoprecipitation showed that EBV-encoded nuclear antigens EBNA-5 and EBNA-3 bind to prolylhydroxylases 1 and 2, respectively, thus inhibiting HIF1A hydroxylation and degradation. Immunostaining and Q-PCR showed that the stabilized HIF1A translocates to the nucleus, forms a heterodimer with ARNT, and transactivates several genes involved in aerobic glycolysis. Using biochemical assays and Q-PCR, we also found that lymphoblastoid cells produce high levels of lactate, lactate dehydrogenase and pyruvate. Conclusions: Our data suggest that activation of the aerobic glycolytic pathway, corresponding to the Warburg effect, occurs in EBV-transformed lymphoblastoid cells, in contrast to mitogen-activated B-cells. | en |
dc.source | Plos One | en |
dc.source.uri | <Go to ISI>://WOS:000306950200156 | |
dc.subject | INDUCIBLE FACTOR-1-ALPHA | en |
dc.subject | GLUCOSE-METABOLISM | en |
dc.subject | EBNA-3 BINDS | en |
dc.subject | HIF-ALPHA | en |
dc.subject | PROTEIN | en |
dc.subject | TUMOR | en |
dc.subject | PATHWAY | en |
dc.subject | COMPLEX | en |
dc.subject | PROLIFERATION | en |
dc.subject | HYDROXYLATION | en |
dc.subject | Multidisciplinary Sciences | en |
dc.title | Epstein-Barr Virus Immortalization of Human B-Cells Leads to Stabilization of Hypoxia-Induced Factor 1 Alpha, Congruent with the Warburg Effect | en |
dc.type | journalArticle | en |
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