Redox-dependent regulation of nuclear import of the glucocorticoid receptor.
A number of transcription factors including the glucocorticoid receptor (GR) are regulated in a redox-dependent fashion. We have previously reported that the functional activity of the GR is suppressed under oxidative conditions and restored in the presence of reducing reagents. In the present study, we have used a chimeric human GR fused to the Aequorea green fluorescent protein and demonstrated that both ligand-dependent and -independent nuclear translocation of the GR is impaired under oxidative conditions in living cells. Substitution of Cys-481 for Ser within NL1 of the human GR resulted in reduction of sensitivity to oxidative treatment, strongly indicating that Cys-481 is one of the target amino acids for redox regulation of the receptor. Taken together, we may conclude that redox-dependent regulation of nuclear translocation of the GR constitutes an important mechanism for modulation of glucocorticoid-dependent signal transduction.
Okamoto
K
K
Second Department of Internal Medicine, Asahikawa Medical College, Nishikagura, Asahikawa 078-8510, Japan.
Tanaka
H
H
Ogawa
H
H
Makino
Y
Y
Eguchi
H
H
Hayashi
S
S
Yoshikawa
N
N
Poellinger
L
L
Umesono
K
K
Makino
I
I
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D016466:CHO Cells; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D006224:Cricetinae; D003545:Cysteine / Q000378:metabolism; D049452:Green Fluorescent Proteins; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008024:Ligands; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D016335:Zinc Fingers
D008024:Ligands; D008164:Luminescent Proteins; D011965:Receptors, Glucocorticoid; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D012694:Serine; D006861:Hydrogen Peroxide; D003545:Cysteine