scholarly journals Analysis of Glycogen Synthase Kinase Inhibitors That Regulate Cytochrome P450 Expression in Primary Human Hepatocytes by Activation of β-Catenin, Aryl Hydrocarbon Receptor and Pregnane X Receptor Signaling

2015 ◽  
Vol 148 (1) ◽  
pp. 261-275 ◽  
Author(s):  
Philippe Briolotti ◽  
Laurent Chaloin ◽  
Patrick Balaguer ◽  
Franck Da Silva ◽  
Veronika Tománková ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Aryl Hydrocarbon Receptor ◽  
Kinase Inhibitors ◽  
Glycogen Synthase ◽  
Pregnane X Receptor ◽  
Human Hepatocytes ◽  
Glycogen Synthase Kinase ◽  
Receptor Signaling ◽  
Aryl Hydrocarbon ◽  
P450 Expression

scholarly journals Glycogen Synthase Kinase 3 Beta Regulates the Human Aryl Hydrocarbon Receptor Cellular Content and Activity

2021 ◽  
Vol 22 (11) ◽  
pp. 6097
Author(s):  
Yujie Yang ◽  
William K. Chan
Keyword(s):  
Protein Degradation ◽  
Aryl Hydrocarbon Receptor ◽  
Gene Transcription ◽  
Target Gene ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Lysosomal Degradation ◽  
Aryl Hydrocarbon ◽  
Cellular Content

The aryl hydrocarbon receptor (AHR) is a cytosolic receptor which is involved in diverse cellular events in humans. The most well-characterized function of AHR is its ability to upregulate gene transcription after exposure to its ligands, such as environmental toxicants, dietary antioxidants, drugs, and endogenous ligands. The cellular content of AHR is partly controlled by its degradation via the ubiquitin–proteasome system and the lysosome-dependent autophagy. We used human cervical cancer (HeLa) cells to investigate how AHR undergoes protein degradation and how its activity is modulated. Since the glycogen synthase kinase 3 beta (GSK3β)-mediated phosphorylation can trigger protein degradation and substrates of GSK3β contain stretches of serine/threonine residues which can be found in AHR, we examined whether degradation and activity of AHR can be controlled by GSK3β. We observed that AHR undergoes the GSK3β-dependent, LC3-mediated lysosomal degradation without ligand treatment. The AHR can be phosphorylated in a GSK3β-dependent manner at three putative sites (S436/S440/S444, S689/S693/T697, and S723/S727/T731), which leads to lysosomal degradation of the AHR protein. Inhibition of the GSK3β activity suppresses the ligand-activated transcription of an AHR target gene in HeLa, human liver cancer (Hep3B), and human breast cancer (MCF-7) cells. Collectively, our findings support that phosphorylation of AHR by GSK3β is essential for the optimal activation of its target gene transcription and this phosphorylation may partake as an “off” switch by subjecting the receptor to lysosomal degradation.

scholarly journals Cannabidiol induces expression of human cytochrome P450 1A1 that is possibly mediated through aryl hydrocarbon receptor signaling in HepG2 cells

Life Sciences ◽  
2015 ◽  
Vol 136 ◽  
pp. 87-93 ◽  
Author(s):  
Satoshi Yamaori ◽  
Yuka Kinugasa ◽  
Rongrong Jiang ◽  
Shuso Takeda ◽  
Ikuo Yamamoto ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Aryl Hydrocarbon Receptor ◽  
Hepg2 Cells ◽  
Receptor Signaling ◽  
Cytochrome P450 1A1 ◽  
Aryl Hydrocarbon ◽  
Human Cytochrome
Sign in / Sign up

Export Citation Format

Share Document