Coenzyme A dependent myristoylation and demyristoylation in the regulation of bovine spleen N-myristoyltransferase.
N-myristoyltransferase (NMT) is an essential eukaryotic enzyme that catalyzes the transfer of myristate to the NH2-terminal glycine residue of a number of important proteins of diverse function. Little is known about the control and regulation of NMT in higher eukaryotes. Bovine spleen N-myristoyltransferase has been purified and characterized [Raju, RVS, Kalra J & Sharma RK (1994) J Biol Chem 269:12080-12083]. The activation of bovine spleen NMT with thiol reducing compounds, and its inhibition by the oxidizing agent sodium iodate, suggest a role for oxidation/reduction in NMT regulation. Available knowledge concerning coenzyme A (CoA), the thiol in the cell, indicated that the agents tested on NMT could also reduce or oxidize CoA. The studies suggested that reduced CoA is the key regulator of NMT activity, while oxidized CoA did not allow NMT to promote myristoylation. Further, the process of myristoylation and demyristoylation may be governed by NMT, depending on the differential concentration of CoA. The process of demyristoylation could be blocked by excess CoA. We therefore hypothesize that the initial event in the regulation of NMT is an increase in cellular CoA concentration which could be coupled to an increase in protein myristoylation. Once the CoA concentration in the cell decreases due to oxidation, the demyristoylation process would be operative.
Raju
R V
RV
Department of Pathology, College of Medicine, University of Saskatchewan, Royal University Hospital, Saskatoon, Canada.
Sharma
R K
RK
D000217:Acyltransferases / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D003065:Coenzyme A / Q000378:metabolism*; D004047:Diethyl Pyrocarbonate / Q000494:pharmacology; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D004789:Enzyme Activation; D007452:Iodates / Q000494:pharmacology; D007460:Iodoacetamide / Q000494:pharmacology; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D013154:Spleen / Q000201:enzymology*; D013439:Sulfhydryl Reagents / Q000494:pharmacology
D007452:Iodates; D009227:Myristic Acids; D013439:Sulfhydryl Reagents; D019814:Myristic Acid; D004228:Dithionitrobenzoic Acid; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase; D004047:Diethyl Pyrocarbonate; D003065:Coenzyme A; D004229:Dithiothreitol; C032285:sodium iodate; D007460:Iodoacetamide