Identification and characterization of eukaryotic initiation factor 5A-2

Paul M.J. Clement, C. Allen Henderson, Zandra A. Jenkins, Zeljka McBride, Edith C. Wolff, John W.B. Hershey, Myung Hee Park, Hans E. Johansson

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

The phylogenetically conserved eukaryotic translation initiation factor 5A (eIF5A) is the only known cellular protein to contain the post-translationally derived amino acid hypusine [Nε-(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 EIF5 A2 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 lack of immunological cross-reactivity, formation of different complexes with deoxyhypusine synthase, and Km values (1.5 ± 0.2 vs. 8.3 ± 1.4 μM for eIF5A-1 and -2, respectively) as substrates for deoxyhypusine synthase in vitro. These physical characteristics and distinct amino acid sequences in the C-terminal domain together with differences in gene expression patterns imply differentiated, tissue-specific functions of the eIF5A-2 isoform in the mammalian organism and in cancer.

Original languageEnglish (US)
Pages (from-to)4254-4263
Number of pages10
JournalEuropean Journal of Biochemistry
Volume270
Issue number21
DOIs
StatePublished - Nov 1 2003

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Eukaryotic Initiation Factor-2
Eukaryotic Initiation Factors
Prokaryotic Initiation Factor-2
Protein Isoforms
Cells
Yeast
Genes
Yeasts
eukaryotic translation initiation factor 5A
Proteins
Amino Acids
Messenger RNA
Cell proliferation
Eukaryotic Cells
Oncogenes
varespladib methyl
Gene expression
Ovarian Neoplasms
Lysine

Keywords

  • Deoxyhypusine
  • eIF5A
  • eIF5A-2
  • Hypusine
  • Polyamines
  • Post-translational modification

ASJC Scopus subject areas

  • Biochemistry

Cite this

Clement, P. M. J., Henderson, C. A., Jenkins, Z. A., McBride, Z., Wolff, E. C., Hershey, J. W. B., ... Johansson, H. E. (2003). Identification and characterization of eukaryotic initiation factor 5A-2. European Journal of Biochemistry, 270(21), 4254-4263. https://doi.org/10.1046/j.1432-1033.2003.03806.x

Identification and characterization of eukaryotic initiation factor 5A-2. / Clement, Paul M.J.; Henderson, C. Allen; Jenkins, Zandra A.; McBride, Zeljka; Wolff, Edith C.; Hershey, John W.B.; Park, Myung Hee; Johansson, Hans E.

In: European Journal of Biochemistry, Vol. 270, No. 21, 01.11.2003, p. 4254-4263.

Research output: Contribution to journalArticle

Clement, PMJ, Henderson, CA, Jenkins, ZA, McBride, Z, Wolff, EC, Hershey, JWB, Park, MH & Johansson, HE 2003, 'Identification and characterization of eukaryotic initiation factor 5A-2', European Journal of Biochemistry, vol. 270, no. 21, pp. 4254-4263. https://doi.org/10.1046/j.1432-1033.2003.03806.x
Clement, Paul M.J. ; Henderson, C. Allen ; Jenkins, Zandra A. ; McBride, Zeljka ; Wolff, Edith C. ; Hershey, John W.B. ; Park, Myung Hee ; Johansson, Hans E. / Identification and characterization of eukaryotic initiation factor 5A-2. In: European Journal of Biochemistry. 2003 ; Vol. 270, No. 21. pp. 4254-4263.
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