, p53, p21 cip1/waf1 , Cdc2, cyclin B1, Chk1, Chk2, and Cdc25C, suggesting that p17 induces a G 2 /M cell cycle arrest through activation of the ATM/p53/p21 cip1/waf1 /Cdc2/cyclin B1 and ATM/Chk1/Chk2/Cdc25C pathways. The G 2 /M cell cycle arrest resulted in increased virus replication. In the present study, we also provide evidence demonstrating that p17 protein is responsible for ARV-induced host cellular protein translation shutoff. Increased phosphorylation levels of the eukaryotic translation elongation factor 2 (eEF2) and initiation factor eIF2␣ and reduced phosphorylation levels of the eukaryotic translation initiation factors eIF4E, eIF4B, and eIF4G, as well as 4E-BP1 and Mnk-1 in p17-transfected cells, demonstrated that ARV p17 suppresses translation initiation factors and translation elongation factors to induce host cellular protein translation shutoff. Inhibition of mTOR by rapamycin resulted in a decrease in the levels of phosphorylated 4E-BP1, eIF4B, and eIF4G and an increase in the levels eEF2 but did not affect ARV replication, suggesting that ARV replication was not hindered by inhibition of cap-dependent translation. Taken together, our data indicate that ARV p17-induced G 2 /M arrest and host cellular translation shutoff resulted in increased ARV replication.
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