Varicella-Zoster Virus IE62 Protein Utilizes the Human Mediator Complex in Promoter Activation
| Autor: | William T. Ruyechan, John Hay, Min Yang |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Transcriptional Activation
Herpesvirus 3 Human viruses Immunology Biology Microbiology Immediate early protein Immediate-Early Proteins MED1 Transactivation Mediator Viral Envelope Proteins Cell Line Tumor Virology Humans Promoter Regions Genetic Mediator Complex Models Genetic Promoter Cyclin-Dependent Kinase 8 Molecular biology Cyclin-Dependent Kinases Genome Replication and Regulation of Viral Gene Expression Protein Transport Insect Science Trans-Activators Cyclin-dependent kinase 8 Chromatin immunoprecipitation Protein Binding |
| Zdroj: | Journal of Virology. 82:12154-12163 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.01693-08 |
| Popis: | The varicella-zoster virus (VZV) major transactivator, IE62, is involved in the expression of all kinetic classes of VZV genes and can also activate cellular promoters, promoters from heterologous viruses, and artificial promoters containing only TATA elements. A key component of the mechanism of IE62 transactivation is an acidic activation domain comprising the N-terminal 86 amino acids of IE62. However, the cellular target of this N-terminal acidic activation is unknown. In the work presented here, we show that the IE62 activation domain targets the human Mediator complex via the Med25 (ARC92) subunit and that this interaction appears to be fundamental for transactivation by the IE62 activation domain. In contrast, the Med23 subunit (Sur2/TRAP150β/DRIP130/CRSP130) of the Mediator complex is not essential for IE62-mediated activation. Further, the IE62 activation domain appears to selectively interact with a form of the Mediator complex lacking CDK8. Chromatin immunoprecipitation experiments showed that IE62 stimulates recruitment of Mediator to an IE62-responsive model promoter. Finally, immunofluorescence microscopy of VZV-infected cells demonstrated intranuclear translocation of the Mediator complex to viral replication compartments. These studies suggest that Mediator is an essential component for efficient VZV gene expression. |
| Databáze: | OpenAIRE |
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