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

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 ca...

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Autores principales: Zhong, Xuelin, Persaud, Leah, Muharam, Hilal, Francis, Ashleigh, Das, Dibash, Aktas, Bertal Huseyin, Sauane, Moira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5977126/
https://www.ncbi.nlm.nih.gov/pubmed/29786657
http://dx.doi.org/10.3390/cancers10050153
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author Zhong, Xuelin
Persaud, Leah
Muharam, Hilal
Francis, Ashleigh
Das, Dibash
Aktas, Bertal Huseyin
Sauane, Moira
author_facet Zhong, Xuelin
Persaud, Leah
Muharam, Hilal
Francis, Ashleigh
Das, Dibash
Aktas, Bertal Huseyin
Sauane, Moira
author_sort Zhong, Xuelin
collection PubMed
description 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 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.
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spelling pubmed-59771262018-05-31 Eukaryotic Translation Initiation Factor 4A Down-Regulation Mediates Interleukin-24-Induced Apoptosis through Inhibition of Translation Zhong, Xuelin Persaud, Leah Muharam, Hilal Francis, Ashleigh Das, Dibash Aktas, Bertal Huseyin Sauane, Moira Cancers (Basel) Article 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 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. MDPI 2018-05-22 /pmc/articles/PMC5977126/ /pubmed/29786657 http://dx.doi.org/10.3390/cancers10050153 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhong, Xuelin
Persaud, Leah
Muharam, Hilal
Francis, Ashleigh
Das, Dibash
Aktas, Bertal Huseyin
Sauane, Moira
Eukaryotic Translation Initiation Factor 4A Down-Regulation Mediates Interleukin-24-Induced Apoptosis through Inhibition of Translation
title Eukaryotic Translation Initiation Factor 4A Down-Regulation Mediates Interleukin-24-Induced Apoptosis through Inhibition of Translation
title_full Eukaryotic Translation Initiation Factor 4A Down-Regulation Mediates Interleukin-24-Induced Apoptosis through Inhibition of Translation
title_fullStr Eukaryotic Translation Initiation Factor 4A Down-Regulation Mediates Interleukin-24-Induced Apoptosis through Inhibition of Translation
title_full_unstemmed Eukaryotic Translation Initiation Factor 4A Down-Regulation Mediates Interleukin-24-Induced Apoptosis through Inhibition of Translation
title_short Eukaryotic Translation Initiation Factor 4A Down-Regulation Mediates Interleukin-24-Induced Apoptosis through Inhibition of Translation
title_sort eukaryotic translation initiation factor 4a down-regulation mediates interleukin-24-induced apoptosis through inhibition of translation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5977126/
https://www.ncbi.nlm.nih.gov/pubmed/29786657
http://dx.doi.org/10.3390/cancers10050153
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