Abstract 3191: The Akt-mTOR axis determines cell fate through the regulation of eIF2α phosphorylation pathway.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Metazoans respond to environmental stress by inducing the phosphorylation of the α subunit of translation initiation factor eIF2at S51 (eIF2αP), a modification that leads to protein synthesis inhibition. We demonstrate that eIF2αP is induced by pharmacological inhibition or genetic ablation of the PI3K-Akt-mTOR pathway([1][1]). Increased eIF2αP is an evolutionary conserved process that involves the endoplasmic reticulum (ER)-resident protein kinase PERK, which is negatively regulated by Akt dependent phosphorylation at T799. The PERK-eIF2αP arm is downregulated by Akt in cells exposed to ER stress or oxidative stress leading to the induction of cell survival or death respectively. In unstressed cells, the PERK-eIF2αP pathway guards survival and facilitates adaptation to the deleterious effects of PI3K, Akt or mTOR inactivation. Inactivation of the PERK-eIF2αP arm sensitizes tumor death from pharmacological inhibition of the PI3K-Akt-mTOR pathway. The PERK-eIF2αP pathway links Akt and mTOR signaling to translational control with implications in tumor treatment with pharmacological inhibitors of PI3K-Akt-mTOR pathway. Citation Format: Clara Tenkerian, ZinebMounir, Jothi Krishnamoorthy, Antonis E. Koromilas. The Akt-mTOR axis determines cell fate through the regulation of eIF2α phosphorylation pathway. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3191. doi:10.1158/1538-7445.AM2013-3191 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend. [1]: #ref-1