| RRC ID |
39318
|
| 著者 |
Ueno M, Masutani H, Arai RJ, Yamauchi A, Hirota K, Sakai T, Inamoto T, Yamaoka Y, Yodoi J, Nikaido T.
|
| タイトル |
Thioredoxin-dependent redox regulation of p53-mediated p21 activation.
|
| ジャーナル |
J Biol Chem
|
| Abstract |
Thioredoxin (TRX) is a dithiol-reducing enzyme that is induced by various oxidative stresses. TRX regulates the activity of DNA-binding proteins, including Jun/Fos and nuclear factor-kappaB. TRX also interacts with an intranuclear reducing molecule redox factor 1 (Ref-1), which enhances the activity of Jun/Fos. Here, we have investigated the role of TRX in the regulation of p53 activity. Electrophoretic mobility shift assay showed that TRX augmented the DNA binding activity of p53 and also further potentiated Ref-1-enhanced p53 activity. Luciferase assay revealed that transfection of TRX enhanced p53-dependent expression of p21 and further intensified Ref-1-mediated p53 activation. Furthermore, Western blot analysis revealed that p53-dependent induction of p21 protein was also facilitated by transfection with TRX. Overexpression of transdominant negative mutant TRX (mTRX) suppressed the effects of TRX or Ref-1, showing a functional interaction between TRX and Ref-1. cis-Diamminedichloroplatinum (II) (CDDP) induced p53 activation and p21 transactivation. The p53-dependent p21 transactivation induced by CDDP was inhibited by mTRX overexpression, suggesting that TRX-dependent redox regulation is physiologically involved in p53 regulation. CDDP also stimulated translocation of TRX from the cytosol into the nucleus. Hence, TRX-dependent redox regulation of p53 activity indicates coupling of the oxidative stress response and p53-dependent repair mechanism.
|
| 巻・号 |
274(50)
|
| ページ |
35809-15
|
| 公開日 |
1999-12-10
|
| DOI |
10.1074/jbc.274.50.35809
|
| PII |
S0021-9258(19)53315-4
|
| PMID |
10585464
|
| MeSH |
Carbon-Oxygen Lyases / metabolism
Cell Nucleus / drug effects
Cell Nucleus / metabolism
Cisplatin / pharmacology
Colonic Neoplasms
Cyclin-Dependent Kinase Inhibitor p21
Cyclins / genetics*
Cyclins / metabolism*
Cytosol / drug effects
Cytosol / metabolism
DNA Repair
DNA-(Apurinic or Apyrimidinic Site) Lyase*
Diamide / pharmacology
Dithiothreitol / pharmacology
Enzyme Inhibitors / metabolism
Homeostasis
Humans
Luciferases / genetics
Oxidation-Reduction
Recombinant Proteins / metabolism
Recombinant Proteins / pharmacology
Thioredoxins / pharmacology*
Transcriptional Activation / drug effects
Transfection
Tumor Cells, Cultured
Tumor Suppressor Protein p53 / metabolism*
|
| IF |
4.238
|
| 引用数 |
343
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
HeLa(RCB0007) |
