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Title of Journal: Amino Acids

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Abbravation: Amino Acids

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Springer Vienna

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DOI

10.1007/s40062-013-0074-z

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1438-2199

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Targeting the polyaminehypusine circuit for the p

Authors: Shima Nakanishi John L Cleveland
Publish Date: 2016/06/29
Volume: 48, Issue: 10, Pages: 2353-2362
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Abstract

The unique amino acid hypusine is present in only two proteins in eukaryotic cells eukaryotic translation initiation factor 5A1 eIF5A1 and eIF5A2 where it is covalently linked to the lysine50 residue of these proteins via a posttranslational modification coined hypusination This unique modification is directed by two highly conserved and essential enzymes deoxyhypusine synthase DHPS and deoxyhypusine hydroxylase DOHH which selectively use the polyamine spermidine as a substrate to generate hypusinated eIF5A Notably elevated levels of polyamines are a hallmark of most tumor types and increased levels of polyamines can also be detected in the urine and blood of cancer patients Further inclinic agents that block the function of key biosynthetic enzymes in the polyamine pathway markedly impair tumor progression and maintenance of the malignant state Thus the polyamine pathway is attractive as a prognostic prevention and therapeutic target As we review recent advances in our understanding of the specific functions of hypusinated eIF5A and its role in tumorigenesis suggest that the polyaminehypusine circuit is a high priority target for cancer therapeutics

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