Myristoylation.
N-myristoylation is an acylation process absolutely specific to the N-terminal amino acid glycine in proteins. This maturation process concerns about a hundred proteins in lower and higher eukaryotes involved in oncogenesis, in secondary cellular signalling, in infectivity of retroviruses and, marginally, of other virus types. Thy cytosolic enzyme responsible for this activity, N-myristoyltransferase (NMT), studied since 1987, has been purified from different sources. However, the studies of the specificities of the various NMTs have not progressed in detail except for those relating to the yeast cytosolic enzyme. Still to be explained are differences in species specificity and between various putative isoenzymes, also whether the data obtained from the yeast enzyme can be transposed to other NMTs. The present review discusses data on the various addressing processes subsequent to myristoylation, a patchwork of pathways that suggests myristoylation is only the first step of the mechanisms by which a protein associates with the membrane. Concerning the enzyme itself, there are evidences that NMT is also present in the endoplasmic reticulum and that its substrate specificity is different from that of the cytosolic enzyme(s). These differences have major implications for their differential inhibition and for their respective roles in several pathologies. For instance, the NMTs from mammalians are clearly different from those found in several microorganisms, which raises the question whether the NMT may be a new targets for fungicides. Finally, since myristoylation has a central role in virus maturation and oncogenesis, specific NMT inhibitors might lead to potent antivirus and anticancer agents.
Boutin
J A
JA
Département de Chemie des Peptides, Institut de Recherches Servier 11, Suresnes, France.
D000215:Acylation; D000217:Acyltransferases / Q000378:metabolism*; D000818:Animals; D006801:Humans; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D013379:Substrate Specificity
D009227:Myristic Acids; D011506:Proteins; D019814:Myristic Acid; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase