title: eEF-2 kinase, another meddler in the "yin and yang" of Akt-mediated cell fate?
abstract: Eukaryotic elongation factor-2 (eEF-2) kinase, also known as calmodulin-dependent protein kinase III, is a unique calcium/calmodulin-dependent enzyme. eEF-2 kinase can act as a negative regulator of protein synthesis and a positive regulator of autophagy under environmental or metabolic stresses. Akt, a key downstream effector of the PI3K signaling pathway that regulates cell survival and proliferation, is an attractive therapeutic target for anticancer treatment. Akt inhibition leads to activation of both apoptosis, type I programmed cell death and autophagy, a cellular degradation process via lysosomal machinery (also termed type II programmed cell death). However, the underlying mechanisms that dictate functional relationship between autophagy and apoptosis in response to Akt inhibition remain to be delineated. Our recent study demonstrated that inhibition of eEF-2 kinase can suppress autophagy but promote apoptosis in tumor cells subjected to Akt inhibition, indicating a role of eEF-2 kinase as a controller in the crosstalk between autophagy and apoptosis. Furthermore, inhibition of eEF-2 kinase can reinforce the efficacy of a novel Akt inhibitor, MK-2206, against human glioma. These findings may help optimize the use of Akt inhibitors in the treatment of cancer and other diseases.
authors: Department of Pharmacology, The Penn State Hershey Cancer Institute, The Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, USA. yxc24@psu.edu
authors: Yan
authors: Y
authors: Cheng
authors: Li
authors: L
authors: Yan
authors: Xingcong
authors: X
authors: Ren
authors: Jin-Ming
authors: JM
authors: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D001343:Autophagy; D001932:Brain Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D019070:Cell Lineage; D002470:Cell Survival; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D005910:Glioma / Q000188:drug therapy; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology; D006801:Humans; D008954:Models, Biological; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019892:eIF-2 Kinase / Q000378:metabolism / Q000502:physiology*
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; C548887:MK 2206; D051057:Proto-Oncogene Proteins c-akt; D019892:eIF-2 Kinase