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

• Published in: Oncogene Vol. 25; no. 12; pp. 1775 - 1785
• Main Authors: Bark-Jones, S J, Webb, H M, West, M J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.03.2006; Nature Publishing; Nature Publishing Group
• Subjects: Alcohol Oxidoreductases; Animals; Apoptosis; Biochemistry; Biological and medical sciences; Blotting, Western; Cell Biology; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Chromatin; Cyclin-Dependent Kinase 9 - drug effects; Cyclin-Dependent Kinase 9 - genetics; Cyclin-Dependent Kinase 9 - metabolism; DNA-Binding Proteins - metabolism; DNA-directed RNA polymerase; Enzyme Inhibitors - pharmacology; Epstein-Barr virus; Epstein-Barr Virus Nuclear Antigens - metabolism; Fundamental and applied biological sciences. Psychology; Herpesvirus 4, Human - physiology; Human Genetics; Humans; Immortalization; Immunoprecipitation; Infections; Internal Medicine; Kinases; Life sciences; Lymphocytes B; Medicine; Medicine & Public Health; Molecular and cellular biology; Molecular genetics; Oncology; original-article; Phosphoproteins - metabolism; Phosphorylation; Phosphorylation - drug effects; Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA polymerase; RNA Polymerase II - metabolism; Serine; Serine - metabolism; Transcription activation; Transcription factors; Transcription, Genetic - drug effects; Transcription. Transcription factor. Splicing. Rna processing; Viral infections; Viral Proteins; CDK9; CTD; serine 2; serine 5; phosphorylation; EBNA 2; Phosphorylation; Transcription; Enzyme; Transferases; Serine; Carcinogenesis; DNA-directed RNA polymerase; Nucleotidyltransferases
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1209205

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- β - 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.