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Translational control of eIF5A in various diseases

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Abstract

Translational control is a crucial component in the development and progression of different diseases. Translational control may involve selective translation of specific mRNAs, which promote cell proliferation or lead to alterations in translation factor levels and activities. Eukaryotic initiation factor 5A (eIF5A) is the only known protein to contain the unusual amino acid hypusine [N ε- (4-amino-2-hydroxybutyl)-lysine], which is formed from the polyamine spermidine by two catalytic steps. eIF5A is involved in translation, elongation and stimulating peptide bond formation. Hypusination of eIF5A is essential for its activity in promoting cell proliferation. Meanwhile, there is evidence that eIF5A is a key protein in the pathogenicity of different diseases, such as diabetes, several human cancers, malaria and HIV-1 infections. Hitherto, the available data suggest that eIF5A has a role of a cell context-dependent function being more proliferative in the case of several human cancers and being involved under stress conditions in diabetes. Secondly, in HIV-1 infections and in diabetes, eIF5A also has a nuclear function by its sequence-specific binding of mRNAs as an mRNA-shuttle in conjunction with nuclear membrane export proteins. This binding may also influence the half-lives of mRNAs or their sequestration. Based on these data, there is a considerable therapeutic interest in eIF5A as a selective target for drug development through inhibition of hypusination.

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Abbreviations

2D-electophoresis:

Two dimensional electrophoresis

MALDI-TOF:

Matrix-assisted laser desorption ionization-time-of-flight

iNos:

Inducible nitric oxide synthase

IL-1β:

Interleukin-1β

TNF-α:

Tumor necrosis factor α

IFN-γ:

Interferon gamma

GTP:

Guanosine triphosphate

GDP:

Guanosine diphosphate

PKR:

Protein kinase R

PERK:

Proline-rich extensin-like receptor protein kinase

GCN2:

General control nonrepressed 2 serine/threonine-protein kinase

Th1-type-cells:

T-helper cells signal 1

Th2-type-cells:

T-helper cells signal 2

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  1. Institut für Technische Chemie und Pharmazeutische Chemie, University of Applied Sciences, Cologne, Betzdorfer Str.2, 50679, Cologne, Germany

    Annette Kaiser

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Kaiser, A. Translational control of eIF5A in various diseases. Amino Acids 42, 679–684 (2012). https://doi.org/10.1007/s00726-011-1042-8

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