Increase in S-adenosylmethionine decarboxylase in SV-3T3 cells treated with S-methyl-5'-methylthioadenosine.
Treatment of SV-3T3 cells with the spermine synthase inhibitor S-methyl-5'-methylthioadenosine [AdoS+(CH3)2] led to a large increase in the activity of S-adenosylmethionine decarboxylase (AdoMetDC) without affecting ornithine decarboxylase. The elevation of AdoMetDC activity was due to an increased amount of enzyme protein, as demonstrated by radioimmunoassay and by immunoblotting. The increase in AdoMetDC protein was caused by at least three factors: an increase in the amount of translatable mRNA, an increased translation efficiency of the mRNA and an increase in the half-life of the protein. The depletion of spermine brought about by AdoS+(CH3)2 appeared to be responsible for the increased synthesis of AdoMetDC and for part of the decrease in its rate of degradation. An additional stabilization of the enzyme protein was probably due to the binding of AdoS+(CH3)2, which is also a weak inhibitor of AdoMetDC. These results demonstrate the importance of cellular spermine concentrations in regulating the activity of AdoMetDC, which is a key enzyme controlling polyamine synthesis.
Pegg
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Department of Physiology, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 17033.
Wechter
R
R
Pajunen
A
A
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors* / Q000235:genetics; D000818:Animals; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D002460:Cell Line; D007122:Immunoelectrophoresis; D011073:Polyamines / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D013872:Thionucleosides / Q000494:pharmacology*
D011073:Polyamines; D012333:RNA, Messenger; D013872:Thionucleosides; C047433:S-methyl-5'-methylthioadenosine; D002262:Carboxy-Lyases; D012437:Adenosylmethionine Decarboxylase; D000241:Adenosine