Regulation of spermidine/spermine N1-acetyltransferase by intracellular polyamine pools. Evidence for a functional role in polyamine homeostasis.
Through its role in polyamine acetylation and the back-conversion pathway, spermidine/spermine N1-acetyltransferase (SSAT) has the potential to control intracellular polyamine pools by facilitating their catabolism and/or excretion. The possibility that the enzyme is subject to regulation by intracellular polyamine pools was investigated in MALME-3 human melanoma cells. Increases in intracellular polyamine pools by treatment with 3 microM exogenous spermidine or spermine for 48 h caused SSAT activity to increase 111% and 226%, respectively, and SSAT-specific mRNA to rise 19% and 66%, respectively. Decreases in polyamine pools by treatment with inhibitors of polyamine biosynthesis caused SSAT activity to decrease by 46% and mRNA to fall by 89%. Both SSAT activity and mRNA were more sensitive to changes in spermine than spermidine. The identification of a positive regulatory relationship between SSAT and intracellular polyamine pools further implicates this enzyme in a proposed model for polyamine pool homeostasis.
Shappell
N W
NW
Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, NY 14263-0001.
Fogel-Petrovic
M F
MF
Porter
C W
CW
D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D015152:Blotting, Northern; D000518:Eflornithine / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006706:Homeostasis; D006801:Humans; D008545:Melanoma; D008954:Models, Biological; D011073:Polyamines / Q000378:metabolism* / Q000494:pharmacology; D011700:Putrescine / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013095:Spermidine / Q000378:metabolism / Q000494:pharmacology; D013096:Spermine / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D000518:Eflornithine; D011073:Polyamines; D011700:Putrescine; D012333:RNA, Messenger; D013095:Spermidine; D013096:Spermine; D000099228:Diamine N-Acetyltransferase