title: RNAi of 14-3-3eta protein increases intracellular stability of tyrosine hydroxylase.
abstract: Tyrosine hydroxylase is the rate-limiting enzyme in catecholamine biosynthesis, and its N-terminus plays a critical role in the intracellular stability of the enzyme. In the present study, we investigated the mechanism by which the N-terminus of human tyrosine hydroxylase type 1 (hTH1) affects the stability. The results obtained by using N-terminus-deleted hTH1 mutants identified the sequence up to Ala(23) as mediating the stability. The down-regulation of 14-3-3eta proteins in PC12D cells exogenously expressing hTH1, enhanced the stability of the wild-type enzyme and that of the mutant lacking the N-terminus up to Ala(23). However, the stability of the mutant was reduced compared to the wild-type enzyme. The stability of the mutant with the N-terminus deleted up to Glu(43) was not affected by the down-regulation of 14-3-3eta. These results suggest that the 14-3-3eta protein regulates hTH1 stability by acting on the N-terminus.
authors: Department of Physiology, School of Medicine, Fujita Health University, Toyoake, Aichi 470-1192, Japan.
authors: Akira
authors: A
authors: Nakashima
authors: Nobuhiro
authors: N
authors: Hayashi
authors: Yoko S
authors: YS
authors: Kaneko
authors: Keiji
authors: K
authors: Mori
authors: Esther L
authors: EL
authors: Sabban
authors: Toshiharu
authors: T
authors: Nagatsu
authors: Akira
authors: A
authors: Ota
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism*; D000409:Alanine / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D034622:RNA Interference; D051381:Rats; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D014446:Tyrosine 3-Monooxygenase; D000409:Alanine