TAILIEUCHUNG - Báo cáo khoa học: Identification and characterization of eukaryotic initiation factor 5A-2

The phylogenetically conserved eukaryotic translation initi-ation factor 5A(eIF5A) is the onlyknown cellular protein to contain thepost-translationallyderivedaminoacidhypusine [N e -(4-amino-2-hydroxybutyl)lysine]. Both eIF5A and its hypusine modification are essential for sustained cell proli-feration. Normally only one eIF5A protein is expressed in human cells. Recently, we identified a second humanEIF5A gene that would encode an isoform (eIF5A-2) of 84% sequence identity. | Eur. J. Biochem. 270 4254-4263 2003 FEBS 2003 doi Identification and characterization of eukaryotic initiation factor 5A-2 Paul M. J. Clement1 C. Allen Henderson2 Zandra A. Jenkins3 4 t Zeljka Smit-McBride2 Edith C. Wolff1 John W. B. Hershey2 Myung Hee Park1 and Hans E. Johansson3 4 1Oral and Pharyngeal Cancer Branch National Institute of Dental and Craniofacial Research National Institutes of Health Bethesda MD USA department of Biological Chemistry School of Medicine University of California at Davis CA USA 3CHORI Children s Hospital Oakland Research Institute Oakland CA USA department of Cell and Molecular Biology Uppsala University Sweden The phylogenetically conserved eukaryotic translation initiation factor 5A eIF5A is the only known cellular protein to contain the post-translationally derived amino acid hypusine Ne- 4-amino-2-hydroxybutyl lysine . Both eIF5A and its hypusine modification are essential for sustained cell proliferation. Normally only one eIF5A protein is expressed in human cells. Recently we identified a second human EIF5A gene that would encode an isoform eIF5A-2 of 84 sequence identity. Overexpression of eIF5A-2 mRNA in certain human cancer cells in contrast to weak normal expression limited to human testis and brain suggests EIF5A2 as a potential oncogene. However eIF5A-2 protein has not been described in human or mammalian cells heretofore. Here we describe the identification of eIF5A-2 protein in human colorectal and ovarian cancer lines SW-480 and UACC-1598 that overexpress eIF5A-2 mRNAs. Functional characterization of the human isoforms revealed that either human EIF5A gene can complement growth of a yeast strain in which the yeast EIF5A genes were disrupted. This indicates functional similarity of the human isoforms in yeast and suggests that eIF5A-2 has an important role in eukaryotic cell survival similar to that of the ubiquitous eIF5A-1. Detectable structural differences were also noted including .

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