Studies on T H E Mode of Action of Diphtheria Toxin* Vi. Site of the Action of Toxin in Living Cells
نویسنده
چکیده
I t has been shown in previous communications that, in the presence of the specific cofactor nicotinamide adenine dinucleotide (NAD), diphtheria toxin inhibits the transfer of amino acids from aminoacyl-tRNA to the growing polypeptide chains on the ribosomes in cell-free extracts from mammalian cells (1). Although bacterial cell extracts axe completely insensitive to inhibition (1), toxin and NAD inhibit amino acid incorporation in cell-free extracts from chick embryonic tissues (2) and from yeast (3). Collier (4) has demonstrated that toxin and NAD act specifically to cause inactivation of the labile peptide bondforming enzyme, transferase II (s). Goor and Pappenheimer (6) also concluded that transferase n was the site of toxin action in cell extracts and noted that only the soluble form was inactivated; the ribosome-bound enzyme was not affected. I t was further observed (3) that the inactivation of transferase II in cell-free systems could be prevented or reversed in the presence of a sufficient concentration of nicotinamide. Finally, it has been found that toxin and NAD interact mole for mole to form a relatively dissociable complex (7, 8). Assuming that this toxin-NAD complex interacts further with transferase II to form an enzymatically inactive product, an equation based on the mass law has been derived that accurately predicts the per cent inhibition of amino acid incorporation in cell-free systems at any given NAD and toxin concentration (3). Although the model we have just described adequately explains the action of toxin in cell-free systems, serious difficulties arise when we attempt to use the model to explain the inhibition by toxin of growth of HeLa cells in culture (3). First, the action of toxin on living HeLa cells is not reversible in the presence of
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تاریخ انتشار 2003