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Peer-reviewedCC BYMolecular oncology

A role for eIF5A in translational control of stress-inducible proteins in multiple myeloma cell lines.

  • Demi Both1,2,3,4
  • Ingrid A M Derks1,2,3,4
  • Raphaël Vanleyssem5
  • Marine Leclercq5
  • Najla El Hachem5
  • Pierre Close5,6
  • Eric Eldering1,2,3,4
  • Marco Vincent Haselager1,2,3,4
6 affiliations
  1. 1Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, The Netherlands.
  2. 2Lymphoma and Myeloma Center Amsterdam, LYMMCARE, Amsterdam, The Netherlands.
  3. 3Cancer Center Amsterdam, Amsterdam, The Netherlands.
  4. 4Amsterdam Infection & Immunity Institute, Amsterdam, The Netherlands.
  5. 5GIGA-Institute, Université de Liège, Liège, Belgium.
  6. 6WELBIO Department, WEL Research Institute, Wavre, Belgium.
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Abstract

Impaired protein folding in the endoplasmic reticulum (ER) causes ER stress and activates the unfolded protein response (UPR), which can induce apoptosis during prolonged ER stress. ER stress is therapeutically targeted in plasma cell malignancies, such as multiple myeloma (MM), but these treatments remain noncurative, and UPR signaling in B-cell malignancies is incompletely understood. A targeted CRISPR-Cas9 screen in RPMI-8226 cells exposed to thapsigargin identified known ER stress regulators (XBP1, IRE1, and calreticulin) and the translation factor eIF5A (eukaryotic translation initiation factor 5A), whose role in ER stress remains unclear. Competition assays showed that eIF5A depletion is detrimental under basal conditions but confers a proliferation advantage during thapsigargin treatment. Inducible EIF5A knockouts confirmed reduced sensitivity specifically to thapsigargin, loss of eIF5A had no or sensitizing effects on cell death induced by other ER stress drugs. Polysome profiling revealed that not general translation, but the translation of specific mRNA transcripts coding for UPR components and apoptotic proteins was affected by eIF5A depletion. Correspondingly, EIF5A KO cells showed reduced thapsigargin-induced UPR activation. In conclusion, these findings indicate that loss of eIF5A alters the stress response in MM cells.

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Cite

BibTeXRIS
BibTeX
@article{both2026role,
  title = {{A role for eIF5A in translational control of stress-inducible proteins in multiple myeloma cell lines.}},
  author = {Demi Both and Ingrid A M Derks and Raphaël Vanleyssem and Marine Leclercq and Najla El Hachem and Pierre Close and Eric Eldering and Marco Vincent Haselager},
  journal = {Molecular oncology},
  year = {2026},
  month = oct,
  doi = {10.1002/1878-0261.70328},
  url = {https://europepmc.org/article/MED/42904597},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - A role for eIF5A in translational control of stress-inducible proteins in multiple myeloma cell lines.
AU  - Demi Both
AU  - Ingrid A M Derks
AU  - Raphaël Vanleyssem
AU  - Marine Leclercq
AU  - Najla El Hachem
AU  - Pierre Close
AU  - Eric Eldering
AU  - Marco Vincent Haselager
PY  - 2026
DA  - 2026/10/21
JO  - Molecular oncology
DO  - 10.1002/1878-0261.70328
UR  - https://europepmc.org/article/MED/42904597
AB  - Impaired protein folding in the endoplasmic reticulum (ER) causes ER stress and activates the unfolded protein response (UPR), which can induce apoptosis during prolonged ER stress. ER stress is therapeutically targeted in plasma cell malignancies, such as multiple myeloma (MM), but these treatments remain noncurative, and UPR signaling in B-cell malignancies is incompletely understood. A targeted CRISPR-Cas9 screen in RPMI-8226 cells exposed to thapsigargin identified known ER stress regulators (XBP1, IRE1, and calreticulin) and the translation factor eIF5A (eukaryotic translation initiation factor 5A), whose role in ER stress remains unclear. Competition assays showed that eIF5A depletion is detrimental under basal conditions but confers a proliferation advantage during thapsigargin treatment. Inducible EIF5A knockouts confirmed reduced sensitivity specifically to thapsigargin, loss of eIF5A had no or sensitizing effects on cell death induced by other ER stress drugs. Polysome profiling revealed that not general translation, but the translation of specific mRNA transcripts coding for UPR components and apoptotic proteins was affected by eIF5A depletion. Correspondingly, EIF5A KO cells showed reduced thapsigargin-induced UPR activation. In conclusion, these findings indicate that loss of eIF5A alters the stress response in MM cells.
SN  - 1574-7891
SN  - 1878-0261
ER  -