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Publication : TCDD induces UbcH7 expression and synphilin-1 protein degradation in the mouse ventral midbrain.

First Author  González-Barbosa E Year  2017
Journal  J Biochem Mol Toxicol Volume  31
Issue  10 PubMed ID  28621812
Mgi Jnum  J:357986 Mgi Id  MGI:6871432
Doi  10.1002/jbt.21947 Citation  Gonzalez-Barbosa E, et al. (2017) TCDD induces UbcH7 expression and synphilin-1 protein degradation in the mouse ventral midbrain. J Biochem Mol Toxicol 31(10)
abstractText  UbcH7 is an ubiquitin-conjugating enzyme that interacts with parkin, an E3 ligase. The UbcH7-parkin complex promotes the ubiquitination and degradation of several proteins via the 26S proteasome. Cellular accumulation of the UbcH7-parkin targets alpha-synuclein and synphilin-1 has been associated with Parkinson disease. In mouse liver, 2,3,7,8-tetrachlorodibenzo-p-dioxin, an aryl hydrocarbon receptor ligand, induces UbcH7 expression. Therefore, the aim of the present study was to determine whether 2,3,7,8-tetrachlorodibenzo-p-dioxin induces Ubch7 mRNA and UbcH7 protein expression in the mouse brain, to characterize the molecular mechanism, and the effect on synphilin-1 half-life. We found that 2,3,7,8-tetrachlorodibenzo-p-dioxin promotes the aryl hydrocarbon receptor binding to Ubch7 gene promoter as well as its transactivation, resulting in an induction of UbcH7 levels in the olfactory bulb, ventral midbrain, hippocampus, striatum, cerebral cortex, brain stem, and medulla oblongata. In parallel, 2,3,7,8-tetrachlorodibenzo-p-dioxin promoted synphilin-1 degradation in an aryl hydrocarbon receptor-dependent way.
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