Inactivation of eukaryotic initiation factor 5A (eIF5A) by specific acetylation of its hypusine residue by spermidine/spermine acetyltransferase 1 (SSAT1)

Seung Bum Lee, Jong Hwan Park, John E. Folk, Jason A. Deck, Anthony E. Pegg, Masaaki Sokabe, Christopher S. Fraser, Myung Hee Park

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

eIF5A (eukaryotic translation initiation factor 5A) is the only cellular protein containing hypusine [Nε-(4-amino-2-hydroxybutyl)lysine]. eIF5A is activated by the post-translational synthesis of hypusine and the hypusine modification is essential for cell proliferation. In the present study, we report selective acetylation of the hypusine and/or deoxyhypusine residue of eIF5A by a key polyamine catabolic enzyme SSAT1 (spermidine/spermine-N 1-acetyltransferase 1). This enzyme normally catalyses the N 1-acetylation of spermine and spermidine to form acetyl-derivatives, which in turn are degraded to lower polyamines. Although SSAT1 has been reported to exert other effects in cells by its interaction with other cellular proteins, eIF5A is the first target protein specifically acetylated by SSAT1. Hypusine or deoxyhypusine, as the free amino acid, does not act as a substrate for SSAT1, suggesting a macromolecular interaction between eIF5A and SSAT1. Indeed, the binding of eIF5A and SSAT1 was confirmed by pull-down assays. The effect of the acetylation of hypusine on eIF5A activity was assessed by comparison of acetylated with non-acetylated bovine testis eIF5A in the methionyl-puromycin synthesis assay. The loss of eIF5A activity by this SSAT1-mediated acetylation confirms the strict structural requirement for the hypusine side chain and suggests a possible regulation of eIF5A by hypusine acetylation/deacetylation.

Original languageEnglish (US)
Pages (from-to)205-213
Number of pages9
JournalBiochemical Journal
Volume433
Issue number1
DOIs
StatePublished - Jan 1 2011

Fingerprint

Eukaryotic Initiation Factors
Acetylation
Acetyltransferases
Spermidine
Spermine
Polyamines
Assays
hypusine
diamine N-acetyltransferase
Puromycin
Proteins
Cell proliferation
Enzymes
Cell Communication
Lysine
Testis
Thermodynamic properties
Cell Proliferation
Derivatives
Amino Acids

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Lee, Seung Bum ; Park, Jong Hwan ; Folk, John E. ; Deck, Jason A. ; Pegg, Anthony E. ; Sokabe, Masaaki ; Fraser, Christopher S. ; Park, Myung Hee. / Inactivation of eukaryotic initiation factor 5A (eIF5A) by specific acetylation of its hypusine residue by spermidine/spermine acetyltransferase 1 (SSAT1). In: Biochemical Journal. 2011 ; Vol. 433, No. 1. pp. 205-213.
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abstract = "eIF5A (eukaryotic translation initiation factor 5A) is the only cellular protein containing hypusine [Nε-(4-amino-2-hydroxybutyl)lysine]. eIF5A is activated by the post-translational synthesis of hypusine and the hypusine modification is essential for cell proliferation. In the present study, we report selective acetylation of the hypusine and/or deoxyhypusine residue of eIF5A by a key polyamine catabolic enzyme SSAT1 (spermidine/spermine-N 1-acetyltransferase 1). This enzyme normally catalyses the N 1-acetylation of spermine and spermidine to form acetyl-derivatives, which in turn are degraded to lower polyamines. Although SSAT1 has been reported to exert other effects in cells by its interaction with other cellular proteins, eIF5A is the first target protein specifically acetylated by SSAT1. Hypusine or deoxyhypusine, as the free amino acid, does not act as a substrate for SSAT1, suggesting a macromolecular interaction between eIF5A and SSAT1. Indeed, the binding of eIF5A and SSAT1 was confirmed by pull-down assays. The effect of the acetylation of hypusine on eIF5A activity was assessed by comparison of acetylated with non-acetylated bovine testis eIF5A in the methionyl-puromycin synthesis assay. The loss of eIF5A activity by this SSAT1-mediated acetylation confirms the strict structural requirement for the hypusine side chain and suggests a possible regulation of eIF5A by hypusine acetylation/deacetylation.",
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Inactivation of eukaryotic initiation factor 5A (eIF5A) by specific acetylation of its hypusine residue by spermidine/spermine acetyltransferase 1 (SSAT1). / Lee, Seung Bum; Park, Jong Hwan; Folk, John E.; Deck, Jason A.; Pegg, Anthony E.; Sokabe, Masaaki; Fraser, Christopher S.; Park, Myung Hee.

In: Biochemical Journal, Vol. 433, No. 1, 01.01.2011, p. 205-213.

Research output: Contribution to journalArticle

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AU - Lee, Seung Bum

AU - Park, Jong Hwan

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AU - Deck, Jason A.

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