HIV transcriptional activation by the accessory protein, VPR, is mediated by the p300 co-activator
| Autor: | Ramu A. Subbramanian, Lisa K. Felzien, Gary J. Nabel, Clive Woffendin, Michael O. Hottiger, Éric A. Cohen |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Gene Expression Regulation
Viral Transcription Genetic viruses Virus Replication Jurkat cells Jurkat Cells Cyclin-dependent kinase CDC2 Protein Kinase Humans CREB-binding protein Nuclear protein Cyclin-dependent kinase 1 Multidisciplinary biology Gene Products vpr Cell Cycle Nuclear Proteins virus diseases vpr Gene Products Human Immunodeficiency Virus Biological Sciences biochemical phenomena metabolism and nutrition Cell cycle CREB-Binding Protein Molecular biology Viral replication HIV-1 Trans-Activators biology.protein Transcription Factors |
| Zdroj: | Proceedings of the National Academy of Sciences. 95:5281-5286 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.95.9.5281 |
| Popis: | The accessory protein, Vpr, is a virion-associated protein that is required for HIV-1 replication in macrophages and regulates viral gene expression in T cells. Vpr causes arrest of cell cycle progression at G 2 /M, presumably through its effect on cyclin B1⋅Cdc2 activity. Here, we show that the ability of Vpr to activate HIV transcription correlates with its ability to induce G 2 /M growth arrest, and this effect is mediated by the p300 transcriptional co-activator, which promotes cooperative interactions between the Rel A subunit of NF-κB and cyclin B1⋅Cdc2. Vpr cooperates with p300, which regulates NF-κB and the basal transcriptional machinery, to increase HIV gene expression. Similar effects are seen in the absence of Vpr with a kinase-deficient Cdc2, and overexpression of p300 increases levels of HIV Vpr + replication. Taken together, these data suggest that p300, through its interactions with NF-κB, basal transcriptional components, and Cdks, is modulated by Vpr and regulates HIV replication. The regulation of p300 by Vpr provides a mechanism to enhance viral replication in proliferating cells after growth arrest by increasing viral transcription. |
| Databáze: | OpenAIRE |
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