Premium
Glycogen Synthase Kinase‐3β Modulation of Basal Aryl Hydrocarbon Receptor Protein Levels in HeLa Cells
Author(s) -
Yang Yujie,
Chan William K.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.826.1
Subject(s) - aryl hydrocarbon receptor , gene knockdown , gsk 3 , downregulation and upregulation , kinase , chemistry , phosphorylation , protein kinase a , signal transduction , microbiology and biotechnology , biology , biochemistry , transcription factor , gene
The aryl hydrocarbon receptor (AHR) is a transcription factor involved in many cellular processes. It has been well accepted that it plays important roles in development, metabolism, immune response, and carcinogenesis. Presently the only known regulation of AHR protein is mediated through proteasomal degradation after ligand activation. In this study, we investigate the mechanisms that govern the AHR protein levels without ligand treatment. The ligand‐free AHR resides in the cytosol and is accompanied by XAP2, Hsp90, and its co‐chaperone p23. We previously discovered that knockdown of p23 can lower the AHR protein levels as well as its message levels. Close examination of the AHR sequence unveils a putative signal for glycogen synthase kinase‐3β (GSK‐3β) phosphorylation which may lead to protein degradation. Treatment of GSK‐3β inhibitors tideglusib and lithium chloride increases the AHR protein levels up to about 2‐fold in wild type HeLa cells but not in p23 knockdown stable HeLa cells. These results suggest that the AHR protein levels can be regulated by GSK‐3β only in the presence of the wild type content of p23. Downregulation of the AHR protein levels by GSK‐3β and p23 appears to be mediated through distinct mechanisms. We will address whether this GSK‐3β effect is p23‐dependent. Additional mechanistic data will be presented to explain the underlying mechanisms. Support or Funding Information NIEHS, R15ES023104 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .