tailieunhanh - Báo cáo y học: "Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein R."

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein R. | Li et al. Retrovirology 2010 7 59 http content 7 1 59 gtr RETR0VIR0L0GY RESEARCH Open Access Cell cycle G2 M arrest through an S phase-dependent mechanism by HIV-1 viral protein R Ge Li 1 Hyeon U Park1 2 Dong Liang1 3 and Richard Y Zhao 1 Abstract Background 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. Results 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 vpt-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. Conclusions 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. Background Human immunodeficiency virus type 1 HIV-1 viral protein R Vpr is a virion-associated accessory

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