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p23 co‐chaperone is essential for the optimal function of the aryl hydrocarbon receptor in Hepa1c1c7 cells by modulating the AhR content
Author(s) -
Nguyen Phuong Minh,
Wang Depeng,
Li Yanjie,
Chan William K
Publication year - 2011
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.25.1_supplement.1007.6
Subject(s) - aryl hydrocarbon receptor , aryl hydrocarbon receptor nuclear translocator , gene knockdown , chemistry , cytoplasm , nuclear receptor , transcription factor , ligand (biochemistry) , receptor , microbiology and biotechnology , biophysics , biochemistry , biology , apoptosis , gene
The aryl hydrocarbon receptor (AhR) is a ligand‐activated, basic helix‐loop‐helix‐PAS transcription factor which involves in xenobiotic metabolism and cell growth. Without ligand, the p23‐containing AhR complex is present in the cytoplasm. Although the roles of p23 for the AhR function were suggested, its necessity has been questioned. Our objective is to investigate whether p23 is necessary for the AhR function in Hepa1c1c7 cells. Using shRNA strategy, we generated the p23‐knockdown Hepa1c1c7 stable (p23KD) cells which contained 30% of the wild type p23 content. When we compared p23KD to the wild type (or negative control knockdown stable) cells, we found that in p23KD cells, the total AhR content was reduced to 60% and the nuclear AhR content after 3MC treatment was also reduced to 50%. The 3MC induction of the CYP1A1 content and the DRE‐driven luciferase activity was significantly less pronounced in p23KD cells. The 3MC‐dependent AhR/Arnt heterodimer in the p23KD nuclear extract bound less DRE than the control nuclear extracts in gel shift assays. However, when we normalized the AhR content, all nuclear extracts bound DRE similarly, even though the p23 content was significantly lowered in the p23KD nuclear extract. We concluded that p23 modulates the cellular AhR content which in turn affects the optimal AhR function upon ligand activation. This work is supported by NIH (WKC, R01ES014050).