Inhibition of aminoacyl-transfer RNA formation by low-molecular substances from melanoma extract.
Two partially purified fractions of the ethanol precipitate (70-95%) of the water extract of Harding-Passey mouse melanoma, which inhibit protein and DNA syntheses of B-16 melanoma cells in culture, also inhibit protein synthesis in various cell-free systems. By examining their inhibitory effects on limited reactions of protein synthesis, it was found that one of them (ME II) inhibits protein synthesis by blocking aminoacyl-tRNA formation, while the other (ME IV) does not. This inhibition of aminoacyl-tRNA formation was not limited to specific amino acids. Since the amino acid-dependent pyrophosphate (PPi)-ATP exchange reaction catalyzed by aminoacyl-tRNA synthetases was not inhibited, it was concluded that some factor(s) in ME II inhibits amino acid transfer from aminoacyl-AMP to tRNA. ME II contains more than 20 proteins from 10,000 to 90,000 daltons. EDTA treatment of this fraction caused the release of low-molecular substances with inhibitory activity from the proteins. The molecular weights of the active substances are less than 5,000 daltons. The active low-molecular substances are apparently not peptides or nucleotides.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000596:Amino Acids / Q000235:genetics*; D000604:Amino Acyl-tRNA Synthetases / Q000037:antagonists & inhibitors; D000818:Animals; D002460:Cell Line; D002474:Cell-Free System; D011756:Diphosphates / Q000378:metabolism; D066298:In Vitro Techniques; D008545:Melanoma / Q000378:metabolism*; D051379:Mice; D008970:Molecular Weight; D010445:Peptide Elongation Factors / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins / Q000302:isolation & purification; D012346:RNA, Transfer, Amino Acyl / Q000096:biosynthesis*; D051381:Rats; D014020:Tissue Extracts / Q000494:pharmacology*
D000596:Amino Acids; D011756:Diphosphates; D010445:Peptide Elongation Factors; D011506:Proteins; D012346:RNA, Transfer, Amino Acyl; D014020:Tissue Extracts; D000255:Adenosine Triphosphate; D000604:Amino Acyl-tRNA Synthetases