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

Lisa K. Felzien, Clive Woffendin, Michael O. Hottiger, Ramu A. Subbramanian, Eric A. Cohen, Gary J. Nabel

Research output: Contribution to journalArticle

Abstract

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 G2/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 G2/M growth arrest, and this effect is mediated by the p300 transcriptional coactivator, 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.

Original languageEnglish (US)
Pages (from-to)5281-5286
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number9
DOIs
StatePublished - Apr 28 1998
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • General

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