Stress induction of the spermidine/spermine N1-acetyltransferase by a post-transcriptional mechanism in mammalian cells.
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 alpha-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 pKa 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.
Gerner
E W
EW
University of Arizona Health Sciences Center, Department of Radiation Oncology, Arizona Cancer Center, Tucson 85724.
Kurtts
T A
TA
Fuller
D J
DJ
Casero
R A
RA
D000107:Acetylation; D000123:Acetyltransferases / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D016466:CHO Cells / Q000378:metabolism; D006224:Cricetinae; D004050:Ditiocarb / Q000494:pharmacology; D000518:Eflornithine / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D006358:Hot Temperature; D006801:Humans; D008175:Lung Neoplasms; D008545:Melanoma; D012333:RNA, Messenger / Q000378:metabolism; D013095:Spermidine / Q000378:metabolism / Q000494:pharmacology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D004050:Ditiocarb; D000518:Eflornithine; D012333:RNA, Messenger; D013095:Spermidine; D000099228:Diamine N-Acetyltransferase