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

79 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Biochemistry

Fingerprint Dive into the research topics of 'Identification and characterization of eukaryotic initiation factor 5A-2'. Together they form a unique fingerprint.

  • Cite this

    Clement, P. M. J., Henderson, C. A., Jenkins, Z. A., McBride, Z., Wolff, E. C., Hershey, J. W. B., Park, M. H., & 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