TY - JOUR
T1 - RNAi of 14-3-3η protein increases intracellular stability of tyrosine hydroxylase
AU - Nakashima, Akira
AU - Hayashi, Nobuhiro
AU - Kaneko, Yoko S.
AU - Mori, Keiji
AU - Sabban, Esther L.
AU - Nagatsu, Toshiharu
AU - Ota, Akira
N1 - Funding Information:
This work was supported by Grants-in-Aid from the Ministry of Education, Science, Sports, and Culture of Japan to A. Nakashima, T. Nagatsu, and A. Ota, and also by a grant from Fujita Health University, Japan, to A. Nakashima.
PY - 2007/11/23
Y1 - 2007/11/23
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbrc.2007.09.042
DO - 10.1016/j.bbrc.2007.09.042
M3 - Article
C2 - 17900529
AN - SCOPUS:34848886827
SN - 0006-291X
VL - 363
SP - 817
EP - 821
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -