The HIV-1 virion-associated protein vpr is a coactivator of the human glucocorticoid receptor.
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.
Kino
T
T
Section on Pediatric Endocrinology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA. kinot@cc1.nichd.nih.gov
Gragerov
A
A
Kopp
J B
JB
Stauber
R H
RH
Pavlakis
G N
GN
Chrousos
G P
GP
D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D016336:Gene Products, vpr / Q000378:metabolism*; D017930:Genes, Reporter / Q000235:genetics; D005938:Glucocorticoids / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D035362:Transcription Factor TFIID; D019473:Transcription Factors, TFII / Q000235:genetics / Q000276:immunology; D015533:Transcriptional Activation / Q000235:genetics*; D014162:Transfection / Q000235:genetics; D014764:Viral Proteins / Q000378:metabolism; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016336:Gene Products, vpr; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D035362:Transcription Factor TFIID; D019473:Transcription Factors, TFII; D014764:Viral Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus; D003907:Dexamethasone