The activity catalyzed by N-myristoyl tranferase (NMT) is described for the first time in microsome-rich fractions from the murine leukemia cell line L1210, rat brain and mouse liver as biological sources. The enzyme from each source can accomodate various types of proteins (protein kinase A, virus structural gag protein or pp60src) as modelized by the use of their N-terminal derived peptides (GNAAAARR, GQTVTTPL and GSSKSKPKDP, respectively).As for some other types of membrane-bound enzymes, NMT activity can be enhanced by pretreatment with various types of detergents, amongst which Triton 770 and deoxycholate were the most potent. Further experiments on the L1210 microsome-rich fractions demonstrate that these two detergents were able to solubilize the microsomal enzyme, without modifying its substrate specificy.Finally, three compounds described in the literature to be inhibitors of NMT activity from other sources were tested for L1210 microsome-associated activity. None of them show any significant potency in inhibiting this activity .A new compound, myristoylphenylalanine, shows a slightly better inhibitory effect on the L1210 microsomal activity than the reference compounds with a median inhibitory concentration (I(&) of 0.2 mM.Myristoylation is a post-translational acylation of proteins catalyzed by NMT [l, 21. From the literature, a growing number of proteins undergo this modification, provided that as an absolute requirement, these proteins bear a glycine at their Nterminus (see [3, 41 for reviews). Amongst the proteins so acylated, three categories can be defined : endogenous proteins (such as protein kinase A, guanyl-nucleotide-binding protein, NADHlcytochrome-b, reductase); oncogene products like pp60v-src, p561ck, p59fyn or p62yes; virus structural proteins such as gag from various types of retrovirus, for example Moloney murine leukemia virus and human immunodefficient virus (see [5, 61 for reviews).Several lines of evidence showed both in virology and cancerology that the suppression by directed mutagenesis of the site of myristoylation leads to (a) the suppression of the transforming potency of pp6Ov-src [7 -91; (b) the assembly of non-infectious viral particles for VPO [lo, 111 and VP1 [12], and (c) the inhibition of viral-particle formation and budding for gag [13-151. Furthermore, numerous viral oncogenes cfes, abl, ras) are expressed in cancerous cell lines as gag-onc fusion proteins which are the active transforming species of the corresponding
