Inhibition of tubulinyl-tyrosine carboxypeptidase by brain soluble RNA and proteoglycan.
Rat brain extracts contain two heat-stable, nondialyzable inhibitors of tubulinyl-tyrosine carboxypeptidase. One of the inhibitors was sensitive to ribonuclease and insensitive to trypsin and pronase, indicating that the inhibitor is RNA. This is supported by the observation that purified RNA from rat brain inhibited the enzyme activity to the same extent as similar amounts of the endogenous RNA. Similar results were obtained with calf liver RNA. The other inhibitor was purified by chromatography on a DEAE-Sephadex and identified as proteoglycan. The elimination of the protein moiety of the proteoglycan resulted in a small increase of its inhibitory activity. Glycosaminoglycan was released from the proteoglycan by beta elimination, indicating that the linkage between glycosaminoglycan and the protein moiety is through an O-glycosidic bond. The glycosaminoglycan contains uronic acid, hexosamine and sulfate in a molar ratio of 1:1.01:0.99, respectively. Treatment of the glycosaminoglycan with chondroitinase ABC completely abolished its inhibitory activity. Chondroitin sulfate A, chondroitin sulfate B, chondroitin sulfate C, and the brain glycosaminoglycan inhibited tubulinyl-tyrosine carboxypeptidase to the same extent when used in comparable amounts.
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors*; D002417:Cattle; D002809:Chondroitin Sulfates / Q000494:pharmacology; D002811:Chondroitinsulfatases / Q000494:pharmacology; D007700:Kinetics; D008099:Liver; D011509:Proteoglycans / Q000502:physiology*; D012313:RNA / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D014404:Tubulin / Q000302:isolation & purification; D050257:Tubulin Modulators; D014443:Tyrosine / Q000037:antagonists & inhibitors
D011509:Proteoglycans; D014404:Tubulin; D050257:Tubulin Modulators; D014443:Tyrosine; D012313:RNA; D002809:Chondroitin Sulfates; D002811:Chondroitinsulfatases; D002268:Carboxypeptidases; C023212:tyrosyltubulin carboxypeptidase