Stress induction of the spermidine/spermine N1-acetyltransferase by a post-transcriptional mechanism in mammalian cells

E. W. Gerner, T. A. Kurtts, D. J.M. Fuller, R. A. Casero

Research output: Contribution to journalArticle

Abstract

Heat shock and diethyldithiocarbamate stimulate polyamine catabolism in animal cells by a mechanism involving the induction of spermidine/spermine N1-acetyltransferase (N1-SSAT) activity. Steady-state levels of RNA encoding this enzyme remain essentially unchanged during periods after these stresses when N1-SSAT activity is increased by 3.5-10-fold or more in three different cell lines of hamster and human origin. Depletion of intracellular spermidine pools by α-difluoromethylornithine (DFMO) inhibits stress induction of N1-SSAT activity. Exogenous spermidine can restore stress inducibility of N1-SSAT to DFMO-treated cells, and induce this enzyme activity in non-heat-shocked but polyamine-depleted cells. Acetylation at N1 suppresses the ability of spermidine to induce N1-SSAT activity, relative to this same modification at N8. Fluorinated spermidine analogues, which decrease the pK(a) values of the amine groups at positions 4 and 8, neither induce nor inhibit N1-SSAT activity in DFMO-treated cells. These data demonstrate that certain stresses induce N1-SSAT by a spermidine-dependent post-transcriptional mechanism. The mode of induction is affected by both the propyl and butyl moieties of spermidine.

Original languageEnglish (US)
Pages (from-to)491-495
Number of pages5
JournalBiochemical Journal
Volume294
Issue number2
DOIs
StatePublished - Jan 1 1993
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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