eIF5A isoforms and cancer: two brothers for two functions?
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Eukaryotic translation initiation factor 5A (eIF5A) is the only cellular protein that contains the unusual amino acid hypusine [N ε-(4-amino-2-hydroxybutyl)lysine]. The role of hypusine formation in the eIF5A protein in the regulation of cell proliferation and apoptosis is addressed in the present review. Moreover, vertebrates carry two genes that encode two eIF5A isoforms, eIF5A-1 and eIF5A-2, which, in humans, are 84% identical. However, the biological functions of these two isoforms may be significantly different. In fact, eIF5A-1 is demonstrable in most cells of different histogenesis, whereas eIF5A-2 protein is detectable only in certain human cancer cells or tissues, suggesting its role as a potential oncogene. In this review we focus our attention on the involvement of eIF5A-1 in the triggering of an apoptotic program and in the regulation of cell proliferation. In addition, the potential oncogenic role and prognostic significance of eIF5A-2 in the prediction of the survival of cancer patients is described. eIF5A-1 and/or the eIF5A-2 isoform may serve as a new molecular diagnostic or prognostic marker or as a molecular target for anti-cancer therapy.
KeywordseIF5A isoform Hypusine Tissue transglutaminase Cancer Apoptosis Prognostic markers Hypusine synthesis inhibitors
This paper is dedicated to the memory of Dr. J.E. Folk (Oct 29, 1925–Dec 27, 2010). In addition to his pioneering work on the mechanism of transglutaminase, he and his colleagues discovered the hypusine modification pathway. The research was supported in part by the Intramural Research Program of National Institute of Dental and Craniofacial Research (NIDCR).
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