| RRC ID |
39347
|
| 著者 |
Makino Y, Yoshikawa N, Okamoto K, Hirota K, Yodoi J, Makino I, Tanaka H.
|
| タイトル |
Direct association with thioredoxin allows redox regulation of glucocorticoid receptor function.
|
| ジャーナル |
J Biol Chem
|
| Abstract |
The glucocorticoid receptor (GR) is considered to belong to a class of transcription factors, the functions of which are exposed to redox regulation. We have recently demonstrated that thioredoxin (TRX), a cellular reducing catalyst, plays an important role in restoration of GR function in vivo under oxidative conditions. Although both the ligand binding domain and other domains of the GR have been suggested to be modulated by TRX, the molecular mechanism of the interaction is largely unknown. In the present study, we hypothesized that the DNA binding domain (DBD) of the GR, which is highly conserved among the nuclear receptors, is also responsible for communication with TRX in vivo. Mammalian two-hybrid assay and glutathione S-transferase pull-down assay revealed the direct association between TRX and the GR DBD. Moreover, analysis of subcellular localization of TRX and the chimeric protein harboring herpes simplex viral protein 16 transactivation domain and the GR DBD indicated that the interaction might take place in the nucleus under oxidative conditions. Together these observations indicate that TRX, via a direct association with the conserved DBD motif, may represent a key mediator operating in interplay between cellular redox signaling and nuclear receptor-mediated signal transduction.
|
| 巻・号 |
274(5)
|
| ページ |
3182-8
|
| 公開日 |
1999-1-29
|
| DOI |
10.1074/jbc.274.5.3182
|
| PII |
S0021-9258(19)88102-4
|
| PMID |
9915858
|
| MeSH |
Animals
Binding Sites
CHO Cells
COS Cells
Cricetinae
DNA / metabolism*
HeLa Cells
Humans
Hydrogen Peroxide / pharmacology
Ligands
Oligodeoxyribonucleotides, Antisense / pharmacology
Oxidation-Reduction
Receptors, Glucocorticoid / metabolism*
Simplexvirus
Thioredoxins / genetics
Thioredoxins / metabolism*
Transcriptional Activation
Viral Proteins / metabolism
|
| IF |
4.238
|
| 引用数 |
157
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
COS-7(RCB0539)
CV-1(RCB0160)
HeLa(RCB0007) |
