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 Ala23 as mediating the stability. The down-regulation of 14-3-3η 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 Ala23. 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 Glu43 was not affected by the down-regulation of 14-3-3η. These results suggest that the 14-3-3η protein regulates hTH1 stability by acting on the N-terminus.
|Number of pages||5|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 23-11-2007|
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology