The HIV-1 Vpr and glucocorticoid receptor complex is a gain-of-function interaction that prevents the nuclear localization of PARP-1 Journal Article
| Authors: | Muthumani, K.; Choo, A. Y.; Zong, W. X.; Madesh, M.; Hwang, D. S.; Premkumar, A.; Thieu, K. P.; Emmanuel, J.; Kumar, S.; Thompson, C. B.; Weiner, D. B. |
| Article Title: | The HIV-1 Vpr and glucocorticoid receptor complex is a gain-of-function interaction that prevents the nuclear localization of PARP-1 |
| Abstract: | The Vpr protein of HIV-1 functions as a vital accessory gene by regulating various cellular functions, including cell differentiation, apoptosis, nuclear factor of κB (NF-κB) suppression and cell-cycle arrest of the host cell. Several reports have indicated that Vpr complexes with the glucocorticoid receptor (GR), but it remains unclear whether the GR pathway is required for Vpr to function. Here, we report that Vpr uses the GR pathway as a recruitment vehicle for the NF-κB co-activating protein, poly(ADP-ribose) polymerase-1 (PARP-1). The GR interaction with Vpr is both necessary and sufficient to facilitate this interaction by potentiating the formation of a Vpr-GR-PARP-1 complex. The recruitment of PARP-1 by the Vpr-GR complex prevents its nuclear localization, which is necessary for Vpr to suppress NF-κB. The association of GR with PARP-1 is not observed with steroid (glucocorticoid) treatment, indicating that the GR association with PARP-1 is a gain of function that is solely attributed to HIV-1 Vpr. These data provide important insights into Vpr biology and its role in HIV pathogenesis. © 2006 Nature Publishing Group. |
| Keywords: | controlled study; protein expression; human cell; mutation; nonhuman; pathophysiology; human immunodeficiency virus infection; protein function; mouse; animals; mice; complex formation; gene expression; cell line; animal experiment; animal model; small interfering rna; protein binding; rna, small interfering; dexamethasone; immunoglobulin enhancer binding protein; in vivo study; transcription factor rela; in vitro study; hela cells; transfection; cercopithecus aethiops; mice, inbred balb c; animalia; gene expression regulation; transcription regulation; tumor necrosis factor-alpha; nf-kappa b; recombinant protein; cellular distribution; active transport, cell nucleus; human immunodeficiency virus; cell nucleus; mifepristone; dna binding; protein interaction mapping; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; receptor binding; hiv infections; human immunodeficiency virus 1; jurkat cells; glucocorticoid receptor; receptors, glucocorticoid; interleukin-1; u937 cells; poly(adp-ribose) polymerases; antigens, bacterial; lipopolysaccharides; i-kappa b proteins; i-kappa b kinase; interleukin-12; adenosine diphosphate ribose; vpr protein; enterotoxins; gene products, vpr |
| Journal Title: | Nature Cell Biology |
| Volume: | 8 |
| Issue: | 2 |
| ISSN: | 1465-7392 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2006-02-01 |
| Start Page: | 170 |
| End Page: | 179 |
| Language: | English |
| DOI: | 10.1038/ncb1352 |
| PUBMED: | 16429131 |
| PROVIDER: | scopus |
| PMCID: | PMC3142937 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 30" - "Export Date: 4 June 2012" - "CODEN: NCBIF" - "Source: Scopus" |
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