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

journal contribution
posted on 2023-06-07, 19:23 authored by S J Bark-Jones, Helen WebbHelen Webb, Michelle WestMichelle West
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.

History

Publication status

  • Published

Journal

Oncogene

ISSN

0950-9232

Issue

12

Volume

25

Page range

1775-1785

Pages

11.0

Department affiliated with

  • Biochemistry Publications

Research groups affiliated with

  • Haematology Research Group Publications

Notes

West's graduate student is first author. Entirely work from West lab. West directed the research and is corresponding author.

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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