Deoxyhypusine synthase haploinsufficiency attenuates acute cytokine signaling

Andrew T. Templin, Bernhard Maier, Yurika Nishiki, Sarah A. Tersey, Raghu Mirmira

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Deoxyhypusine synthase (DHS) catalyzes the post-translational formation of the amino acid hypusine. Hypusine is unique to the eukaryotic translational initiation factor 5A (eIF5A), and is required for its functions in mRNA shuttling, translational elongation and stress granule formation. In recent studies, we showed that DHS promotes cytokine and ER stress signaling in the islet β cell and thereby contributes to its dysfunction in the setting of diabetes mellitus. Here, we review the evidence supporting a role for DHS (and hypusinated eIF5A) in cellular stress responses, and provide new data on the phenotype of DHS knockout mice. We show that homozygous knockout mice are embryonic lethal, but heterozygous knockout mice appear normal with no evidence of growth or metabolic deficiencies. Mouse embryonic fibroblasts from heterozygous knockout mice attenuate acute cytokine signaling, as evidenced by reduced production of inducible nitric oxide synthase, but show no statistically significant defects in proliferation or cell cycle progression. Our data are discussed with respect to the utility of sub-maximal inhibition of DHS in the setting of inflammatory states, such as diabetes mellitus.

Original languageEnglish
Pages (from-to)1043-1049
Number of pages7
JournalCell Cycle
Volume10
Issue number7
DOIs
StatePublished - Apr 1 2011

Fingerprint

Haploinsufficiency
Knockout Mice
Cytokines
Eukaryotic Initiation Factors
Diabetes Mellitus
Nitric Oxide Synthase Type II
Islets of Langerhans
Cell Cycle
Fibroblasts
deoxyhypusine synthase
Phenotype
Amino Acids
Messenger RNA
Growth

Keywords

  • Cytokine
  • Diabetes
  • Hypusine
  • Inflammation
  • mRNA translation
  • Posttranslational modification

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Deoxyhypusine synthase haploinsufficiency attenuates acute cytokine signaling. / Templin, Andrew T.; Maier, Bernhard; Nishiki, Yurika; Tersey, Sarah A.; Mirmira, Raghu.

In: Cell Cycle, Vol. 10, No. 7, 01.04.2011, p. 1043-1049.

Research output: Contribution to journalArticle

Templin, Andrew T. ; Maier, Bernhard ; Nishiki, Yurika ; Tersey, Sarah A. ; Mirmira, Raghu. / Deoxyhypusine synthase haploinsufficiency attenuates acute cytokine signaling. In: Cell Cycle. 2011 ; Vol. 10, No. 7. pp. 1043-1049.
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