title: Serine protease inhibitors block N-terminal arginylation of proteins by inhibiting the arginylation of tRNA in rat brains.
abstract: The tRNA mediated, posttranslational, N-terminal arginylation of proteins occurs in all eukaryotic cells. In nervous tissue, these reactions can be inhibited by endogenous molecules with a molecular weight of between one thousand and five thousand. In the present experiments, exogenous serine protease inhibitors (10(-5) M or less) but not other types of protease inhibitors, were found to be able to block the arginylation of protein in extracts of rat brain homogenates. Inhibition was not by the usual mode of action of protease inhibitors, but by interfering (non-competitively) with the charging of tRNA. Since arginylated proteins are rapidly ubiquitinated and degraded by cytosolic proteases, serine protease inhibitors may act to stabilize proteins by a dual mechanism of inhibiting arginylation as well as inhibiting serine proteases.
authors.affiliation: Department of Physiology, New Jersey Medical School, Newark 07103-2757.
authors.forename: M
authors.initials: M
authors.lastname: Yu
authors.forename: G
authors.initials: G
authors.lastname: Chakraborty
authors.forename: M
authors.initials: M
authors.lastname: Grabow
authors.forename: N A
authors.initials: NA
authors.lastname: Ingoglia
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000502:physiology*; D012347:RNA, Transfer, Arg / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*
chemical_list: D009419:Nerve Tissue Proteins; D012347:RNA, Transfer, Arg; D015842:Serine Proteinase Inhibitors; D001120:Arginine; D008239:Lysine