The HIV-1 Vpr and glucocorticoid receptor complex is a gain-of-function interaction that prevents the nuclear localization of PARP-1

Karuppiah Muthumani, Andrew Y. Choo, Wei Xing Zong, Muniswamy Madesh, Daniel S. Hwang, Arumugam Premkumar, Khanh P. Thieu, Joann Emmanuel, Sanjeev Kumar, Craig B. Thompson, David B. Weiner

Research output: Contribution to journalArticle

51 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)170-179
Number of pages10
JournalNature Cell Biology
Volume8
Issue number2
DOIs
StatePublished - Feb 2006
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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    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. (2006). The HIV-1 Vpr and glucocorticoid receptor complex is a gain-of-function interaction that prevents the nuclear localization of PARP-1. Nature Cell Biology, 8(2), 170-179. https://doi.org/10.1038/ncb1352