Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Sci. Signal., 27 September 2011
Vol. 4, Issue 192, p. ra62
Increasing the Chances of Death
Regulation of mRNA translation affects cell growth, proliferation, and differentiation and involves several eukaryotic initiation factors (eIFs). Cells respond to various stresses by blocking the initiation of translation through the phosphorylation of the eIF2α subunit by a number of kinases, including PERK. Increased signaling by the kinases phosphoinositide 3-kinase (PI3K) and Akt is commonly observed in human cancers and leads to the phosphorylation of several proteins involved in the regulation of cell survival and proliferation. Mounir et al. found that the activity of PERK and the amount of phosphorylated eIF2α (eIF2αP) were increased in cells deficient in Akt signaling. The authors showed that Akt-mediated phosphorylation of PERK inhibited its activity and blocked the phosphorylation of eIF2α. In cells undergoing oxidative or endoplasmic reticulum stress, the PERK-eIF2αP pathway antagonized the activity of Akt. Finally, blocking the PERK-eIF2αP pathway rendered tumor cells more susceptible to death after treatment with inhibitors of PI3K-Akt signaling. These data suggest that Akt can control protein synthesis through the PERK-eIF2αP pathway and that inactivation of PERK and eIF2αP may improve the efficacy of therapies that target PI3K-Akt signaling.
Citation: Z. Mounir, J. L. Krishnamoorthy, S. Wang, B. Papadopoulou, S. Campbell, W. J. Muller, M. Hatzoglou, A. E. Koromilas, Akt Determines Cell Fate Through Inhibition of the PERK-eIF2α Phosphorylation Pathway. Sci. Signal.4, ra62 (2011).