Eukaryotic translation initiation factor 5A (eIF5A) is essential for HIF-1α activation in hypoxia

Biochemical and Biophysical Research Communications
Mohammad TariqMinoru Yoshida

Abstract

The eukaryotic initiation factor 5A (eIF5A) is an essential protein involved in translation elongation and cell proliferation. eIF5A undergoes several post-translational modifications including hypusination and acetylation. Hypusination is indispensable for the function of eIF5A. On the other hand, the precise function of acetylation remains unknown, but it may render the protein inactive since hypusination blocks acetylation. Here, we report that acetylation of eIF5A increases under hypoxia. During extended hypoxic periods an increase in the level of eIF5A acetylation correlated with a decrease in HIF-1α, suggesting involvement of eIF5A activity in HIF-1α expression under hypoxia. Indeed, suppression of eIF5A by siRNA oligo-mediated knockdown or treatment with GC7, a deoxyhypusine synthase inhibitor, led to significant reduction of HIF-1α activity. Furthermore, knockdown of eIF5A or GC7 treatment reduced tumor spheroid formation with a concomitant decrease in HIF-1α expression. Our results suggest that functional, hypusinated eIF5A is necessary for HIF-1α expression during hypoxia and that eIF5A is an attractive target for cancer therapy.

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Citations

May 14, 2020·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Sebastien GiraudThierry Hauet
May 6, 2020·Amino Acids·Annette KaiserJames Thujon Njuguna
Oct 16, 2020·International Journal of Molecular Sciences·Safiah Ibrahim AlthurwiFazlul Huq

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