Intracellular stability of tyrosine hydroxylase: phosphorylation and proteasomal digestion of the enzyme.
Tyrosine hydroxylase (TH), the rate-limiting enzyme in the biosynthesis of catecholamines, is a key protein involved in the pathogenesis of neurodegenerative diseases such as Parkinson's disease. Elucidation of the mechanisms regulating the synthesis, degradation, and activity of TH should be a first target in order to understand the role of this enzyme in pathogenesis. Recently, several reports suggest that the ubiquitin-proteasome pathway is a prerequisite for the degradation of TH and that the N-terminal part of TH plays a critical role in the degradation. In this report, we propose the mechanism by which the N-terminal part of TH regulates the degradation of this enzyme. Moreover, we integrate our findings with recent progress in other areas of TH regulation.
Department of Physiology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan. Electronic address: anakashi@fujita-hu.ac.jp.
Akira
A
Nakashima
Yoko S
YS
Kaneko
Yu
Y
Kodani
Keiji
K
Mori
Hiroshi
H
Nagasaki
Toshiharu
T
Nagatsu
Akira
A
Ota
D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D002395:Catecholamines; D014446:Tyrosine 3-Monooxygenase; D046988:Proteasome Endopeptidase Complex
14-3-3 Protein; Intracellular stability; Phosphorylation; Proteasomal digestion; Tyrosine hydroxylase