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 language | English (US) |
|---|---|
| Pages (from-to) | 4254-4263 |
| Number of pages | 10 |
| Journal | European Journal of Biochemistry |
| Volume | 270 |
| Issue number | 21 |
| DOIs | |
| State | Published - Nov 1 2003 |
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Keywords
- Deoxyhypusine
- eIF5A
- eIF5A-2
- Hypusine
- Polyamines
- Post-translational modification
ASJC Scopus subject areas
- Biochemistry
Cite this
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 journal › Article
}
TY - JOUR
T1 - Identification and characterization of eukaryotic initiation factor 5A-2
AU - Clement, Paul M.J.
AU - Henderson, C. Allen
AU - Jenkins, Zandra A.
AU - McBride, Zeljka
AU - Wolff, Edith C.
AU - Hershey, John W.B.
AU - Park, Myung Hee
AU - Johansson, Hans E.
PY - 2003/11/1
Y1 - 2003/11/1
N2 - 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.
AB - 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.
KW - Deoxyhypusine
KW - eIF5A
KW - eIF5A-2
KW - Hypusine
KW - Polyamines
KW - Post-translational modification
UR - http://www.scopus.com/inward/record.url?scp=0242331088&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0242331088&partnerID=8YFLogxK
U2 - 10.1046/j.1432-1033.2003.03806.x
DO - 10.1046/j.1432-1033.2003.03806.x
M3 - Article
C2 - 14622290
AN - SCOPUS:0242331088
VL - 270
SP - 4254
EP - 4263
JO - FEBS Journal
JF - FEBS Journal
SN - 1742-464X
IS - 21
ER -