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(NL4-3)-infected T-cells. Mutation of Pro-35, which is important for the integrity of helix-α1 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: Institute of Virology, University of Erlangen-Nuremberg, Erlangen 91054, Germany. Stefan.Soergel@viro.med.uni-erlangen.de
authors: Stefan
authors: S
authors: Sörgel
authors: Kirsten
authors: K
authors: Fraedrich
authors: Jörg
authors: J
authors: Votteler
authors: Marco
authors: M
authors: Thomas
authors: Thomas
authors: T
authors: Stamminger
authors: Ulrich
authors: U
authors: Schubert
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival; D016195:G2 Phase / Q000187:drug effects*; D015497:HIV-1 / Q000378:metabolism; D006367:HeLa Cells / Q000821:virology; D006801:Humans; D019169:Jurkat Cells / Q000821:virology; D009685:Nuclear Envelope / Q000378:metabolism*; D014162:Transfection; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1; D053148:Caspase 3