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.
University of Arizona Health Sciences Center, Department of Radiation Oncology, Arizona Cancer Center, Tucson 85724.
E W
EW
Gerner
T A
TA
Kurtts
D J
DJ
Fuller
R A
RA
Casero
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