DEGRADATION OF TYROSINE AMINOTRANSFERASE (TAT) VIA THE UBIQUITIN-PROTEASOME PATHWAY

Most of the known cellular substrates of the ubiquitin system are shor t-lived growth regulators and transcriptional activators. Very few enz ymes involved in intermediary metabolism have been shown to be targete d by the system. In a reconstituted cell-free system, we show that tyr osine aminotransferase (TAT), a key enzyme involved in amino acid meta bolism, is conjugated and degraded in an ATP- and ubiquitin-dependent manner. Degradation of ubiquitin-TAT adducts requires, in addition to the 26S proteasome, a novel, yet unidentified, factor, TAT can be prot ected from degradation by association with its coenzyme pyridoxal phos phate. To examine the potential role of the ubiquitin system in regula ting the stability of the enzyme in vivo, we show that cell extracts d erived from livers of animals in which TAT was induced, display a coro llary increase in the formation of specific TAT-ubiquitin adducts. (C) 1997 Federation of European Biochemical Societies.