Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein R
<p>Abstract</p> <p>Background</p> <p>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 bee...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-07-01
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| Series: | Retrovirology |
| Online Access: | http://www.retrovirology.com/content/7/1/59 |
| _version_ | 1818084237334544384 |
|---|---|
| author | Liang Dong Park Hyeon U Li Ge Zhao Richard Y |
| author_facet | Liang Dong Park Hyeon U Li Ge Zhao Richard Y |
| author_sort | Liang Dong |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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 Ser<sup>345 </sup>phosphorylation in an S phase-dependent manner. The S phase-dependent requirement of Chk1-Ser<sup>345 </sup>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-Ser<sup>345 </sup>phosphorylation and G2 arrest. Even though hydroxyurea (HU) and ultraviolet light (UV) also induce Chk1-Ser<sup>345 </sup>phosphorylation in S phase under the same conditions, neither HU nor UV-treated cells were able to pass through S phase, whereas <it>vpr</it>-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.</p> <p>Conclusions</p> <p>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.</p> |
| first_indexed | 2024-12-10T19:50:42Z |
| format | Article |
| id | doaj.art-72f879917329406282690c055110dd79 |
| institution | Directory Open Access Journal |
| issn | 1742-4690 |
| language | English |
| last_indexed | 2024-12-10T19:50:42Z |
| publishDate | 2010-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Retrovirology |
| spelling | doaj.art-72f879917329406282690c055110dd792022-12-22T01:35:48ZengBMCRetrovirology1742-46902010-07-01715910.1186/1742-4690-7-59Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein RLiang DongPark Hyeon ULi GeZhao Richard Y<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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 Ser<sup>345 </sup>phosphorylation in an S phase-dependent manner. The S phase-dependent requirement of Chk1-Ser<sup>345 </sup>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-Ser<sup>345 </sup>phosphorylation and G2 arrest. Even though hydroxyurea (HU) and ultraviolet light (UV) also induce Chk1-Ser<sup>345 </sup>phosphorylation in S phase under the same conditions, neither HU nor UV-treated cells were able to pass through S phase, whereas <it>vpr</it>-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.</p> <p>Conclusions</p> <p>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.</p>http://www.retrovirology.com/content/7/1/59 |
| spellingShingle | Liang Dong Park Hyeon U Li Ge Zhao Richard Y Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein R Retrovirology |
| title | Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein R |
| title_full | Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein R |
| title_fullStr | Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein R |
| title_full_unstemmed | Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein R |
| title_short | Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein R |
| title_sort | cell cycle g2 m arrest through an s phase dependent mechanism by hiv 1 viral protein r |
| url | http://www.retrovirology.com/content/7/1/59 |
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