EBV EBNA 2 stimulates CDK9-dependent transcription and RNA polymerase II phosphorylation on serine 5

Bark-Jones, S J, Webb, H M and West, M J (2006) EBV EBNA 2 stimulates CDK9-dependent transcription and RNA polymerase II phosphorylation on serine 5. Oncogene, 25 (12). pp. 1775-1785. ISSN 0950-9232

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Abstract

EBNA 2 is one of only five viral genes essential for the infection and immortalization of human B cells by the cancer-associated virus Epstein-Barr virus (EBV). EBNA 2 activates cellular and viral transcription and associates with components of the basal transcription apparatus and a number of coactivators. We provide the first evidence to show that the mechanism of transcriptional activation by EBNA 2 also involves phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (pol II). We found that transcriptional activation by EBNA 2 was inhibited by a dominant-negative mutant of the pol II CTD kinase, CDK9, and by low concentrations of the CDK9 inhibitor 5, 6-dichloro-1-ß-D-ribofuranosylbenzimidazole. Moreover, using chromatin immunoprecipitation assays we demonstrated that EBNA 2 stimulates both pol II recruitment and pol II phosphorylation on serine 5 of the CTD in vivo. These results identify a new step in the transcription cycle that is subject to regulation by a key EBV-encoded transcription factor and highlight CDK9 inhibitors as potential anti-EBV agents.

Item Type: Article
Additional Information: West's graduate student is first author. Entirely work from West lab. West directed the research and is corresponding author.
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Helen Webb - Biochemistry
Date Deposited: 06 Feb 2012 18:15
Last Modified: 04 May 2012 08:48
URI: http://sro.sussex.ac.uk/id/eprint/15480
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