Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein R.
Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein R.
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DOI：
10.1186/1742-4690-7-59
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发表时间：
2010-07-07
期刊：
影响因子：
3.3
通讯作者：
Zhao RY
中科院分区：
文献类型：
--
作者：
Li G;Park HU;Liang D;Zhao RY
Cell cycle G2 arrest induced by HIV-1 Vpr is thought to benefit viral proliferation by providing an optimized cellular environment for viral replication and by skipping host immune responses. Even though Vpr-induced G2 arrest has been studied extensively, how Vpr triggers G2 arrest remains elusive. To examine this initiation event, we measured the Vpr effect over a single cell cycle. We found that even though Vpr stops the cell cycle at the G2/M phase, but the initiation event actually occurs in the S phase of the cell cycle. Specifically, Vpr triggers activation of Chk1 through Ser345 phosphorylation in an S phase-dependent manner. The S phase-dependent requirement of Chk1-Ser345 phosphorylation by Vpr was confirmed by siRNA gene silencing and site-directed mutagenesis. Moreover, downregulation of DNA replication licensing factors Cdt1 by siRNA significantly reduced Vpr-induced Chk1-Ser345 phosphorylation and G2 arrest. Even though hydroxyurea (HU) and ultraviolet light (UV) also induce Chk1-Ser345 phosphorylation in S phase under the same conditions, neither HU nor UV-treated cells were able to pass through S phase, whereas vpr-expressing cells completed S phase and stopped at the G2/M boundary. Furthermore, unlike HU/UV, Vpr promotes Chk1- and proteasome-mediated protein degradations of Cdc25B/C for G2 induction; in contrast, Vpr had little or no effect on Cdc25A protein degradation normally mediated by HU/UV. These data suggest that Vpr induces cell cycle G2 arrest through a unique molecular mechanism that regulates host cell cycle regulation in an S-phase dependent fashion.
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影响因子：
3.3
作者：
Caly L;Saksena NK;Piller SC;Jans DA
通讯作者：
Jans DA
影响因子：
8
作者：
Chaturvedi, P;Eng, WK;Zhou, BBS
通讯作者：
Zhou, BBS
DOI：
10.1006/scel.1993.1051
发表时间：
1993-12-01
期刊：
Seminars in cell biology
影响因子：
--
作者：
Atherton-Fessler, S;Hannig, G;Piwnica-Worms, H
通讯作者：
Piwnica-Worms, H
影响因子：
2.8
作者：
Cans, C;Ducommun, B;Baldin, V
通讯作者：
Baldin, V
影响因子：
2.3
作者：
Fujita M
通讯作者：
Fujita M