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

Xuelin Zhong1,2, Leah Persaud3,4, Hilal Muharam5

  • 1Department of Biological Sciences, Herbert H. Lehman College, City University of New York, 250 Bedford Park Boulevard West, Bronx, NY 10468, USA. xzhong@gradcenter.cuny.edu.

Cancers
|May 23, 2018
PubMed

Insights

Interleukin 24 (IL-24) inhibits the helicase eIF4A, selectively reducing translation of survival-related mRNAs. This mechanism underlies IL-24

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Signaling

Background:

  • Dysregulated eukaryotic initiation factor 4A (eIF4A) activity promotes cancer development by altering protein translation.
  • Interleukin 24 (IL-24) is a tumor suppressor protein with anti-cancer properties, including apoptosis induction and inhibition of angiogenesis.

Purpose of the Study:

  • To investigate the mechanism by which IL-24 exerts its tumor-suppressing effects, specifically its interaction with eIF4A.
  • To elucidate the role of eIF4A in IL-24-mediated apoptosis and identify key signaling pathways involved.

Main Methods:

  • Assessed the effect of IL-24 on eIF4A activity in cancer cells.
  • Analyzed the translation of mRNAs with structured 5'-untranslated regions (5'UTRs) under IL-24 treatment.
  • Investigated the role of eIF4A and Sigma 1 Receptor in IL-24-induced mitochondrial depolarization and apoptosis.

Main Results:

  • IL-24 directly inhibits eIF4A activity.
  • IL-24 treatment selectively reduces the translation of mRNAs with structured 5'UTRs, which encode proteins involved in cell survival and proliferation.
  • Overexpression of eIF4A confers resistance to IL-24-induced cell death, while IL-24 induces eIF4A-dependent and Sigma 1 Receptor-dependent mitochondrial depolarization, leading to apoptosis.

Conclusions:

  • IL-24 suppresses cancer cell phenotype by inhibiting eIF4A and selectively reducing the translation of pro-survival factors.
  • The Sigma 1 Receptor is involved in IL-24-mediated eIF4A down-regulation and subsequent apoptosis.
  • IL-24 triggers apoptosis through a complex regulatory pathway involving eIF4A and mitochondrial function.
Keywords:
Interleukin 24Sigma 1 receptorapoptosiseukaryotic initiation factor 4Aeukaryotic initiation factor 4F complextranslation regulation

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