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Deoxyhypusine synthase, an essential enzyme for hypusine biosynthesis, is required for proper exocrine pancreas

Leah R Padgett1, Morgan A Robertson2, Emily K Anderson-Baucum1

  • 1Indiana Biosciences Research Institute, Indianapolis, IN, USA.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|April 3, 2021
PubMed

Insights

Deoxyhypusine synthase (DHPS) and eukaryotic initiation factor 5A (eIF5A) are crucial for pancreatic acinar cell development. Their absence leads to acinar cell loss, impacting pancreatic function and disease therapies.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Gastroenterology

Background:

  • Pancreatic diseases like diabetes necessitate therapies to restore cellular mass.
  • Identifying molecular pathways regulating cellular growth is key for therapeutic development.
  • Deoxyhypusine synthase (DHPS) activates eukaryotic initiation factor 5A (eIF5A), a translation factor.

Purpose of the Study:

  • To investigate the role of DHPS and eIF5A in pancreatic organogenesis.
  • To elucidate the link between DHPS, eIF5A, and pancreatic acinar cell development.

Main Methods:

  • Conditional deletion of Dhps and Eif5a genes in murine pancreas.
  • Assessment of pancreatic acinar cell presence and development.
  • Evaluation of mRNA translation and protein synthesis.

Main Results:

  • Conditional deletion of Dhps or Eif5a resulted in the absence of pancreatic acinar cells.
  • DHPS/eIF5A deficiency caused defective mRNA translation.
  • Impaired protein synthesis critical for cellular development was observed.

Conclusions:

  • DHPS and eIF5A are essential for pancreatic acinar cell development and survival.
  • This pathway is critical for synthesizing proteins required for pancreatic cellular function.
  • Findings offer insights into potential therapeutic targets for pancreatic diseases.
Keywords:
DHPSacinar cellseIF5Aexocrine pancreashypusine biosynthesismRNA translationtranslational regulation

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