skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Perinuclear localization of the HIV-1 regulatory protein Vpr is important for induction of G2-arrest

Abstract

The HIV-1 accessory protein Vpr induces G2 cell cycle arrest and apoptosis. Previous studies indicate that the induction of G2-arrest requires the localization of Vpr to the nuclear envelope. Here we show that treatment of Vpr-expressing HeLa cells with the caspase 3 inhibitor Z-DEVD-fmk induced accumulation of Vpr at the nuclear lamina, while other proteins or structures of the nuclear envelope were not influenced. Furthermore, Z-DEVD-fmk enhances the Vpr-mediated G2-arrest that even occurred in HIV-1{sub NL4-3}-infected T-cells. Mutation of Pro-35, which is important for the integrity of helix-{alpha}1 in Vpr, completely abrogated the Z-DEVD-fmk-mediated accumulation of Vpr at the nuclear lamina and the enhancement of G2-arrest. As expected, inhibition of caspase 3 reduced the induction of apoptosis by Vpr. Taken together, we could show that besides its role in Vpr-mediated apoptosis induction caspase 3 influences the localization of Vpr at the nuclear envelope and thereby augments the Vpr-induced G2-arrest.

Authors:
 [1];  [1];  [1];  [2];  [1];  [1];  [1]
  1. Institute of Virology, University of Erlangen-Nuremberg, Erlangen 91054 (Germany)
  2. (United States)
Publication Date:
OSTI Identifier:
22150073
Resource Type:
Journal Article
Journal Name:
Virology
Additional Journal Information:
Journal Volume: 432; Journal Issue: 2; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0042-6822
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AIDS VIRUS; APOPTOSIS; CELL CYCLE; DNA DAMAGES; FLUORESCENCE; HELA CELLS; MACROPHAGES; MONOCYTES; PROLINE; PROTEINS; TETRAZOLIUM

Citation Formats

Soergel, Stefan, E-mail: Stefan.Soergel@viro.med.uni-erlangen.de, Fraedrich, Kirsten, E-mail: Kirsten.Fraedrich@viro.med.uni-erlangen.de, Votteler, Joerg, E-mail: Joerg.Votteler@biochem.utah.edu, Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, Thomas, Marco, E-mail: Marco.Thomas@viro.med.uni-erlangen.de, Stamminger, Thomas, E-mail: Thomas.Stamminger@viro.med.uni-erlangen.de, and Schubert, Ulrich, E-mail: ulrich.schubert@viro.med.uni-erlangen.de. Perinuclear localization of the HIV-1 regulatory protein Vpr is important for induction of G2-arrest. United States: N. p., 2012. Web. doi:10.1016/J.VIROL.2012.06.027.
Soergel, Stefan, E-mail: Stefan.Soergel@viro.med.uni-erlangen.de, Fraedrich, Kirsten, E-mail: Kirsten.Fraedrich@viro.med.uni-erlangen.de, Votteler, Joerg, E-mail: Joerg.Votteler@biochem.utah.edu, Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, Thomas, Marco, E-mail: Marco.Thomas@viro.med.uni-erlangen.de, Stamminger, Thomas, E-mail: Thomas.Stamminger@viro.med.uni-erlangen.de, & Schubert, Ulrich, E-mail: ulrich.schubert@viro.med.uni-erlangen.de. Perinuclear localization of the HIV-1 regulatory protein Vpr is important for induction of G2-arrest. United States. doi:10.1016/J.VIROL.2012.06.027.
Soergel, Stefan, E-mail: Stefan.Soergel@viro.med.uni-erlangen.de, Fraedrich, Kirsten, E-mail: Kirsten.Fraedrich@viro.med.uni-erlangen.de, Votteler, Joerg, E-mail: Joerg.Votteler@biochem.utah.edu, Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, Thomas, Marco, E-mail: Marco.Thomas@viro.med.uni-erlangen.de, Stamminger, Thomas, E-mail: Thomas.Stamminger@viro.med.uni-erlangen.de, and Schubert, Ulrich, E-mail: ulrich.schubert@viro.med.uni-erlangen.de. Thu . "Perinuclear localization of the HIV-1 regulatory protein Vpr is important for induction of G2-arrest". United States. doi:10.1016/J.VIROL.2012.06.027.
@article{osti_22150073,
title = {Perinuclear localization of the HIV-1 regulatory protein Vpr is important for induction of G2-arrest},
author = {Soergel, Stefan, E-mail: Stefan.Soergel@viro.med.uni-erlangen.de and Fraedrich, Kirsten, E-mail: Kirsten.Fraedrich@viro.med.uni-erlangen.de and Votteler, Joerg, E-mail: Joerg.Votteler@biochem.utah.edu and Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT and Thomas, Marco, E-mail: Marco.Thomas@viro.med.uni-erlangen.de and Stamminger, Thomas, E-mail: Thomas.Stamminger@viro.med.uni-erlangen.de and Schubert, Ulrich, E-mail: ulrich.schubert@viro.med.uni-erlangen.de},
abstractNote = {The HIV-1 accessory protein Vpr induces G2 cell cycle arrest and apoptosis. Previous studies indicate that the induction of G2-arrest requires the localization of Vpr to the nuclear envelope. Here we show that treatment of Vpr-expressing HeLa cells with the caspase 3 inhibitor Z-DEVD-fmk induced accumulation of Vpr at the nuclear lamina, while other proteins or structures of the nuclear envelope were not influenced. Furthermore, Z-DEVD-fmk enhances the Vpr-mediated G2-arrest that even occurred in HIV-1{sub NL4-3}-infected T-cells. Mutation of Pro-35, which is important for the integrity of helix-{alpha}1 in Vpr, completely abrogated the Z-DEVD-fmk-mediated accumulation of Vpr at the nuclear lamina and the enhancement of G2-arrest. As expected, inhibition of caspase 3 reduced the induction of apoptosis by Vpr. Taken together, we could show that besides its role in Vpr-mediated apoptosis induction caspase 3 influences the localization of Vpr at the nuclear envelope and thereby augments the Vpr-induced G2-arrest.},
doi = {10.1016/J.VIROL.2012.06.027},
journal = {Virology},
issn = {0042-6822},
number = 2,
volume = 432,
place = {United States},
year = {2012},
month = {10}
}