Post-translational arginylation and intracellular proteolysis.
Cellular proteins may be designated to fast degradation by their N-terminal amino acids, and especially a N-terminal arginine residue should have an extremely destabilizing effect on cytosol proteins. We investigated the post-translational arginylation of cytosol proteins and especially of ornithine decarboxylase (ODC) by the cytosolic enzyme arginyl transferase by incubation with radioactive L-arginyl-tRNA and isolation of ODC with our monoclonal antibody. Arginylated ODC had a specific radioactivity 8600 times that of the bulk of cytosolic proteins and Edman-degradation of this ODC showed that the post-translational arginylation occurred only at the L-amino-end of the enzyme. The inhibitor of arginyltransferase, L-Glutamyl-L-Valyl-L-Phenylalanine, increased the half-life of ODC in cultured hepatocytes from 39 min to more than 90 min. This post-translational arginylation of ODC and also of other cytosol proteins is reversible. At least 25 different cytosol proteins in addition to ODC can be arginylated in hepatocytes, and at least 15 different proteins can be arginylated in Dictyostelium discoideum. The arginylated proteins are much more rapidly degraded by cellular proteinases, especially by calpains, than those cytosolic proteins which are not arginylated.
Bohley
P
P
Physiologisch-chemisches Institut, Eberhard-Karls-Universität, Tübingen, Germany.
Kopitz
J
J
Adam
G
G
Rist
B
B
von Appen
F
F
Urban
S
S
D000217:Acyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000595:Amino Acid Sequence; D019881:Aminoacyltransferases; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism*
D009842:Oligopeptides; D011506:Proteins; C073546:glutamyl-valyl-phenylalanine; D001120:Arginine; D000217:Acyltransferases; D019881:Aminoacyltransferases; C019727:arginyltransferase; D010447:Peptide Hydrolases; D009955:Ornithine Decarboxylase