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Thioredoxin-dependent Redox Regulation of p53-mediated p21 Activation
Open accessAbstract
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.
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Cites
Crystal Structure of a p53 Tumor Suppressor-DNA Complex: Understanding Tumorigenic Mutations
Cho, Y., Gorina, S., Jeffrey, P. D., & Pavletich, N. P. (1994) · Science · doi:10.1126/science.8023157 · Cited by 2,551
Cited by
Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling
Ray, P. D., Huang, B.-W., & Tsuji, Y. (2012) · Cellular Signalling · doi:10.1016/j.cellsig.2012.01.008 · Cited by 4,373
Radical-free biology of oxidative stress
Jones, D. P. (2008) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00283.2008 · Cited by 1,213
Thioredoxin and Related Molecules–From Biology to Health and Disease
Lillig, C. H., & Holmgren, A. (2007) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.9.25 · Cited by 724
Hanschmann, E.-M., Godoy, J. R., Berndt, C., Hudemann, C., & Lillig, C. H. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4599 · Cited by 677
The thioredoxin system in cancer
Arnér, E. S. J., & Holmgren, A. (2006) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2006.10.009 · Cited by 589
Metadata
- Authors
- Ueno, M., Masutani, H., Arai, R. J., Yamauchi, A., Hirota, K., Sakai, T., Inamoto, T., Yamaoka, Y., Yodoi, J., & Nikaido, T.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-12
- Volume
- 274
- Issue
- 50
- Pages
- 35809-35815
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2023971274
- Cited by
- 428
- References
- 1
- FWCI
- 7.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Ueno, M., Masutani, H., Arai, R. J., Yamauchi, A., Hirota, K., Sakai, T., Inamoto, T., Yamaoka, Y., Yodoi, J., & Nikaido, T. (1999). Thioredoxin-dependent Redox Regulation of p53-mediated p21 Activation. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.274.50.35809
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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