HIV transcriptional activation by the accessory protein, VPR, is mediated by the p300 co-activator

Proceedings of the National Academy of Sciences of the United States of America - Tập 95 Số 9 - Trang 5281-5286 - 1998
Lisa K. Felzien1, Clive Woffendin1, Michael O. Hottiger1, Ramu A. Subbramanian1, Éric A. Cohen1, Gary J. Nabel1
1Departments of Internal Medicine and Biological Chemistry, Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, MI 48109-0650; and Laboratoire de Rétrovirologie Humaine, Département de Microbiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, H3C 3J7 Québec, Canada

Tóm tắt

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.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 95 Số 9

5281-5286

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