The HIV-1 virion-associated protein vpr is a coactivator of the human glucocorticoid receptor.
The HIV-1 virion-associated protein vpr is a coactivator of the human glucocorticoid receptor.
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HIV-1 病毒粒子相关蛋白 vpr 是人类糖皮质激素受体的共激活剂。
DOI：
10.1084/jem.189.1.51
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发表时间：
1999-01-04
影响因子：
15.3
通讯作者：
Chrousos, G P
中科院分区：
文献类型：
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作者：
Kino, T;Gragerov, A;Kopp, J B;Stauber, R H;Pavlakis, G N;Chrousos, G P
HIV-1病毒体相关辅助蛋白Vpr影响病毒复制和细胞转录、增殖和分化。我们报告说，Vpr增强活性的糖皮质激素在淋巴和肌肉来源的细胞系直接相互作用的糖皮质激素受体和一般的转录因子，作为一种共激活剂。Vpr含有也存在于细胞核受体辅激活因子中的特征基序LXXLL，例如类固醇受体辅激活因子1和p300/CREB结合蛋白，其介导它们与糖皮质激素和其他核激素受体的相互作用。一个突变Vpr分子与破坏这个共激活子签名基序失去了影响糖皮质激素反应基因的转录的能力，并成为一个显性负性Vpr抑制剂，可能是通过保留其一般的转录因子结合活性。Vpr的糖皮质激素辅激活因子活性可能有助于在没有皮质醇增多症的情况下增加组织糖皮质激素敏感性和AIDS的发病机制。
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.