Eukaryotic Translation Initiation Factor 4A Down-Regulation Mediates Interleukin-24-Induced Apoptosis through Inhibition of Translation

Authors

Xuelin Zhong, CUNY Graduate CenterFollow
Leah Persaud, CUNY Lehman CollegeFollow
Hilal Muharam, CUNY Lehman CollegeFollow
Ashleigh Francis, CUNY Lehman CollegeFollow
Dibash Das, CUNY Graduate CenterFollow
Bertal Huseyin Atkas, Brigham and Women's Hospital
Moire Sauane, CUNY Lehman CollegeFollow

Document Type

Article

Publication Date

5-22-2018

Abstract

Dysregulated activity of helicase eIF4A drives transformation to and maintenance of cancer cell phenotype by reprogramming cellular translation. Interleukin 24 (IL-24) is a tumor-suppressing protein, which has the ability to inhibit angiogenesis, sensitize cancer cells to chemotherapy, and induce cancer cell-specific apoptosis. In this study, we found that eIF4A is inhibited by IL-24. Consequently, selective reduction of translation was observed for mRNAs harboring strong secondary structures in their 50 -untranslated regions (50UTRs). These mRNAs encode proteins, which function in cell survival and proliferation. Consistently, overexpression of eIF4A conferred cancer cells with resistance to IL-24-induced cell death. It has been established that inhibition of eIF4A triggers mitochondrial-mediated apoptosis. We showed that IL-24 induces eIF4A-dependent mitochondrial depolarization. We also showed that IL-24 induces Sigma 1 Receptor-dependent eIF4A down-regulation and mitochondrial depolarization. Thus, the progress of apoptosis triggered by IL-24 is characterized by a complex program of changes in regulation of several initiation factors, including the eIF4A.

Comments

This article was originally published in Cancers, available at doi:10.3390/cancers10050153.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY 4.0) license (http://creativecommons.org/licenses/by/4.0/).