Aging
Navigate
Submit an Article
Research Paper|Volume 2, Issue 10|pp 669—677

HDAC pharmacological inhibition promotes cell death through the eIF2α kinases PKR and GCN2

Philippos Peidis1, Andreas I. Papadakis1,2, Kamindla Rajesh1, Antonis E. Koromilas1,3
  • 1Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada
  • 2Division of Experimental Medicine, Faculty of Medicine, McGill University, Montreal, Quebec H3A 1A3, Canada
  • 3Department of Oncology, Faculty of Medicine, McGill University, Montreal, Quebec H2W 1S6, Canada
* These authors contributed equally
Received: September 14, 2010Accepted: October 29, 2010Published: October 31, 2010
https://doi.org/10.18632/aging.100216

Copyright: © 2010 Peidis et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Histone deacetylase inhibitors (HDACi) comprise a family of chemotherapeutic agents used in the clinic to treat cutaneous T-cell lymphoma and tested for the therapy of other malignancies. Previous reports have shown that eIF2α phosphorylation is induced upon treatment with HDACi. However the kinase responsible for this phosphorylation or the biological significance of this finding is not yet established. Herein, we show that eIF2α phosphorylation is not attributed to a specific eIF2α kinase, but rather different eIF2α kinases contribute to its upregulation in response to the HDACi, vorinostat. More importantly our data indicate that eIF2α phosphorylation acts in a cytoprotective manner, whereas the eIF2α kinases PKR and GCN2 promote vorinostat-induced apoptosis. These results reveal a dual nature for eIF2α kinases with potential implications in the treatment with histone deacetylase inhibitors.