The HIV-1 virion-associated protein Vpr is a coactivator of the human glucocorticoid receptor

Tomoshige Kino, Alexander Gragerov, Jeffrey B. Kopp, Roland H. Stauber, George N. Pavlakis, George P. Chrousos

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175 Citations (Scopus)

Abstract

The HIV-1 virion-associated accessory protein Vpr affects both viral replication and cellular transcription, proliferation, and differentiation. We report that Vpr enhances the activity of glucocorticoids in lymphoid and muscle-derived cell lines by interacting directly with the glucocorticoid receptor and general transcription factors, acting as a coactivator. Vpr contains the signature motif LXXLL also present in cellular nuclear receptor coactivators, such as steroid receptor coactivator 1 and p300/CREB-binding protein, which mediates their interaction with the glucocorticoid and other nuclear hormone receptors. A mutant Vpr molecule with disruption of this coactivator signature motif lost its ability to influence transcription of glucocorticoid-responsive genes and became a dominant-negative inhibitor of Vpr, possibly by retaining its general transcription factor-binding activities. The glucocorticoid coactivator activity of Vpr may contribute to increased tissue glucocorticoid sensitivity in the absence of hypercortisolism and to the pathogenesis of AIDS.

Original languageEnglish
Pages (from-to)51-61
Number of pages11
JournalJournal of Experimental Medicine
Volume189
Issue number1
DOIs
Publication statusPublished - 4 Jan 1999
Externally publishedYes

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Keywords

  • AIDS
  • Mouse mammary tumor virus
  • Nuclear receptors
  • p300/CBP
  • Steroid receptor coactivator 1

ASJC Scopus subject areas

  • Immunology

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