Revisiting an old acquaintance: role for eIF5A in diabetes
Joachim Hauber
Joachim Hauber
Published May 24, 2010
Citation Information: J Clin Invest. 2010;120(6):1806-1808. https://doi.org/10.1172/JCI43237.
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Commentary

Revisiting an old acquaintance: role for eIF5A in diabetes

Abstract

Dysfunction of pancreatic islet β cells underlies both type 1 and type 2 diabetes and appears to result in part from the local release of proinflammatory cytokines. An improved understanding of the mechanisms that mediate islet responsiveness to proinflammatory cytokines may therefore expand our knowledge of the role of cytokine signaling in the development of diabetes, providing potential new targets for the development of therapeutics to protect pancreatic islets from inflammation. In this issue of the JCI, Maier and colleagues identify eukaryotic translation initiation factor 5A (eIF5A) as a critical regulator of the inflammatory response in mouse pancreatic islets. I believe these data provide new and important insights into the regulatory pathways that contribute to the development of diabetes and deepen our understanding of the function of the, so far, rather enigmatic cellular protein eIF5A.

Authors

Joachim Hauber

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Figure 1

Hypusine modification of eIF5A.

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Hypusine modification of eIF5A. The enzymes DHS and DOHH catalyze hypusi...
The enzymes DHS and DOHH catalyze hypusine modification of eIF5A. DHS catalyzes the transfer of the aminobutyl moiety of the polyamine spermidine to the ε-NH2 group of Lys50 in the inactive eIF5A precursor protein. This intermediate is subsequently hydroxylated by DOHH, resulting in hypusine modification and the formation of active eIF5A. DHS has been efficiently targeted by low-molecular-weight drugs, such as the spermidine analogue GC7 (24) and the multivalent guanylhydrazone CNI-1493 (14). The metalloenzyme DOHH has been targeted by iron-chelating compounds, such as mimosine and deferiprone (25).