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

Kino T, Gragerov A, Kopp JB, Stauber RH, Pavlakis GN, Chrousos GP - J. Exp. Med. (1999)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Section on Pediatric Endocrinology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA. kinot@cc1.nichd.nih.gov

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.

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A model of the involvement of Vpr in glucocorticoid-dependent activation of transcription. Vpr enhances the glucocorticoid response  by direct association with components of the glucocorticoid-induced  transcription initiation complex, including the GR itself and TFIIB. Interactions with p300/CBP and SRC-1 are also possible. This function of  Vpr is similar to that of other known mammalian coactivators.
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Figure 7: A model of the involvement of Vpr in glucocorticoid-dependent activation of transcription. Vpr enhances the glucocorticoid response by direct association with components of the glucocorticoid-induced transcription initiation complex, including the GR itself and TFIIB. Interactions with p300/CBP and SRC-1 are also possible. This function of Vpr is similar to that of other known mammalian coactivators.

Mentions: These results suggest that Vpr functions by bridging the ligand-bound nuclear receptor and general transcription factors, resulting in the stabilization of the transcription preinitiation complex. It is also highly probable that Vpr cooperates with and enhances the activity of other coactivators, the same way coactivators cooperate with each other. We found synergistic effects of Vpr with both p300 and SRC-1 on the MMTV promoter (Fig. 6). The simplest interpretation of these results is that each coactivator, including Vpr, contributes to the efficiency and stability of the transcription initiation complex (Fig. 7).


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

Kino T, Gragerov A, Kopp JB, Stauber RH, Pavlakis GN, Chrousos GP - J. Exp. Med. (1999)

A model of the involvement of Vpr in glucocorticoid-dependent activation of transcription. Vpr enhances the glucocorticoid response  by direct association with components of the glucocorticoid-induced  transcription initiation complex, including the GR itself and TFIIB. Interactions with p300/CBP and SRC-1 are also possible. This function of  Vpr is similar to that of other known mammalian coactivators.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1887689&req=5

Figure 7: A model of the involvement of Vpr in glucocorticoid-dependent activation of transcription. Vpr enhances the glucocorticoid response by direct association with components of the glucocorticoid-induced transcription initiation complex, including the GR itself and TFIIB. Interactions with p300/CBP and SRC-1 are also possible. This function of Vpr is similar to that of other known mammalian coactivators.
Mentions: These results suggest that Vpr functions by bridging the ligand-bound nuclear receptor and general transcription factors, resulting in the stabilization of the transcription preinitiation complex. It is also highly probable that Vpr cooperates with and enhances the activity of other coactivators, the same way coactivators cooperate with each other. We found synergistic effects of Vpr with both p300 and SRC-1 on the MMTV promoter (Fig. 6). The simplest interpretation of these results is that each coactivator, including Vpr, contributes to the efficiency and stability of the transcription initiation complex (Fig. 7).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Section on Pediatric Endocrinology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA. kinot@cc1.nichd.nih.gov

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.

Show MeSH
Related in: MedlinePlus