The HIV-1 Virion-associated Protein Vpr Is a Coactivator of the Human Glucocorticoid Receptor

نویسندگان

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

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.

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عنوان ژورنال:
  • The Journal of Experimental Medicine

دوره 189  شماره 

صفحات  -

تاریخ انتشار 1999