DJ-1 regulates tyrosine hydroxylase expression through CaMKK?/CaMKIV/CREB1 pathway in vitro and in vivo.
Lack of dopamine production and neurodegeneration of dopaminergic neurons in the substantia nigra are considered as the major characteristics of Parkinson's disease, a prevalent movement disorder worldwide. DJ-1 mutation leading to loss of its protein functions is a genetic factor of PD. In this study, our results illustrated that DJ-1 ... can directly interact with Ca2+ /calmodulin-dependent protein kinase kinase ? (CaMKK?) and modifies the cAMP-responsive element binding protein 1 (CREB1) activity, thus regulates tyrosine hydroxylase (TH) expression. In Dj-1 knockout mouse substantia nigra, the levels of TH and the phosphorylation of CREB1 Ser133 are significantly decreased. Moreover, Dj-1 deficiency suppresses the phosphorylation of CaMKIV (Thr196/200) and CREB1 (Ser133), subsequently inhibits TH expression in vitro. Furthermore, Knockdown of Creb1 abolishes the effects of DJ-1 on TH regulation. Our data reveal a novel pathway in which DJ-1 regulates CaMKK?/CaMKIV/CREB1 activities to facilitate TH expression.
Mesh Terms:
Animals, Calcium-Calmodulin-Dependent Protein Kinase Kinase, Calcium-Calmodulin-Dependent Protein Kinase Type 4, Cell Line, Tumor, Cyclic AMP Response Element-Binding Protein, HEK293 Cells, HeLa Cells, Humans, Mice, Mice, Knockout, Parkinson Disease, Phosphorylation, Protein Deglycase DJ-1, Signal Transduction, Substantia Nigra, Tyrosine 3-Monooxygenase
Animals, Calcium-Calmodulin-Dependent Protein Kinase Kinase, Calcium-Calmodulin-Dependent Protein Kinase Type 4, Cell Line, Tumor, Cyclic AMP Response Element-Binding Protein, HEK293 Cells, HeLa Cells, Humans, Mice, Mice, Knockout, Parkinson Disease, Phosphorylation, Protein Deglycase DJ-1, Signal Transduction, Substantia Nigra, Tyrosine 3-Monooxygenase
J Cell Physiol
Date: Dec. 01, 2019
PubMed ID: 31232473
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