Zhong, XuelinPersaud, LeahMuharam, HilalFrancis, AshleighDas, DibashAktas, Bertal HuseyinSauane, Moira2018-06-272018Zhong, Xuelin, Leah Persaud, Hilal Muharam, Ashleigh Francis, Dibash Das, Bertal Huseyin Aktas, and Moira Sauane. 2018. “Eukaryotic Translation Initiation Factor 4A Down-Regulation Mediates Interleukin-24-Induced Apoptosis through Inhibition of Translation.” Cancers 10 (5): 153. doi:10.3390/cancers10050153. http://dx.doi.org/10.3390/cancers10050153.http://nrs.harvard.edu/urn-3:HUL.InstRepos:37160172Dysregulated 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 5′-untranslated regions (5′UTRs). 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.en-USInterleukin 24eukaryotic initiation factor 4F complexeukaryotic initiation factor 4ASigma 1 receptortranslation regulationapoptosisJournal Article2018-06-2710.3390/cancers10050153