Perinuclear localization of the HIV-1 regulatory protein Vpr is important for induction of G2-arrest.
Perinuclear localization of the HIV-1 regulatory protein Vpr is important for induction of G2-arrest.
复制标题
HIV-1 调节蛋白 Vpr 的核周定位对于诱导 G2 阻滞非常重要。
DOI：
10.1016/j.virol.2012.06.027
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Schubert,Ulrich
中科院分区：
文献类型：
--
作者：
Sorgel,Stefan;Fraedrich,Kirsten;Votteler,Jorg;Thomas,Marco;Stamminger,Thomas;Schubert,Ulrich
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-1NL4–3-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.
