9-cis-retinoic acid decreases the level of its cognate receptor, retinoid X receptor, through acceleration of the turnover.
In this study, we investigated the ligand-mediated regulation of retinoid X receptor (RXR) in two human cell lines (HepG2 and JEG-3 cells), which have been reported to express RXRalpha predominantly. Western blot analysis revealed that a treatment with 1 microM 9-cis-retinoic acid (9-cis RA) for 24 h decreased RXRalpha protein level to 72 +/- 9 and 75 +/- 7% in HepG2 and JEG-3 cells, respectively, when the levels in the non-treated cells were expressed as 100%. The decrease was not due to the changes in steady-state level of RXRalpha mRNA or its stability as revealed by Northern blot analysis. However, the 9-cis RA treatment decreased the half-life of RXRalpha protein as determined by pulse-chase analysis. It was thus demonstrated that 9-cis RA downregulates RXRalpha by increasing the turnover of the protein in the two cell lines. The ligand-dependent downregulation of RXRalpha protein may be important for several hormonal signalings, in which the receptors heterodimerize with RXR.
Division of Molecular and Cellular Adaptation, Nagoya University, Nagoya, 464-8601, Japan.
Y
Y
Nomura
T
T
Nagaya
Y
Y
Hayashi
F
F
Kambe
H
H
Seo
D000077556:Alitretinoin; D015152:Blotting, Northern; D015153:Blotting, Western; D003609:Dactinomycin / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D047488:Retinoid X Receptors; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D019384:Nucleic Acid Synthesis Inhibitors; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D003609:Dactinomycin; D000077556:Alitretinoin; D014212:Tretinoin