Thioredoxin2 enhances the damaged DNA binding activity of mtTFA through direct interaction

Akihiko Kidani, Hiroto Izumi, Yoichiro Yoshida, Eiji Kashiwagi, Haruki Ohmori, Tsuneo Tanaka, Michihiko Kuwano, Kimitoshi Kohno

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Mitochondrial transcription factor A (mtTFA) is a member of the HMG (high mobility group)-box protein family. We previously showed that mtTFA preferentially binds to both cisplatin-damaged and oxidatively damaged DNA. In this study, we found that expression levels of both mtTFA and the mitochondrial antioxidant protein thioredoxin2 (TRX2) are upregulated in cisplatin-resistant cell lines. In addition, TRX2 directly interacts with mtTFA and enhances its damaged DNA binding activity. The interaction between mtTFA and TRX2 requires the HMG box 1 motif of mtTFA. Furthermore, when amino acid substitutions were introduced at either C49G or C246stop, TRX2 interacted with mtTFA. However, the interaction of TRX2 with mtTFA was enhanced when both mutations (C49G and C246stop) were introduced. Binding to cisplatin-damaged DNA was similar among mutant mtTFA proteins. By contrast, binding to oxidized DNA was significantly enhanced when double mutations were introduced. These results suggest that TRX2 not only functions as an antioxidant, but also supports mtTFA functions.

Original languageEnglish
Pages (from-to)1435-1440
Number of pages6
JournalInternational Journal of Oncology
Volume35
Issue number6
DOIs
Publication statusPublished - Dec 1 2009
Externally publishedYes

Fingerprint

DNA
Cisplatin
HMGB Proteins
Antioxidants
mitochondrial transcription factor A
Mutation
Mitochondrial Proteins
Amino Acid Substitution
Cell Line
Proteins

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Thioredoxin2 enhances the damaged DNA binding activity of mtTFA through direct interaction. / Kidani, Akihiko; Izumi, Hiroto; Yoshida, Yoichiro; Kashiwagi, Eiji; Ohmori, Haruki; Tanaka, Tsuneo; Kuwano, Michihiko; Kohno, Kimitoshi.

In: International Journal of Oncology, Vol. 35, No. 6, 01.12.2009, p. 1435-1440.

Research output: Contribution to journalArticle

Kidani, A, Izumi, H, Yoshida, Y, Kashiwagi, E, Ohmori, H, Tanaka, T, Kuwano, M & Kohno, K 2009, 'Thioredoxin2 enhances the damaged DNA binding activity of mtTFA through direct interaction', International Journal of Oncology, vol. 35, no. 6, pp. 1435-1440. https://doi.org/10.3892/ijo-00000462
Kidani, Akihiko ; Izumi, Hiroto ; Yoshida, Yoichiro ; Kashiwagi, Eiji ; Ohmori, Haruki ; Tanaka, Tsuneo ; Kuwano, Michihiko ; Kohno, Kimitoshi. / Thioredoxin2 enhances the damaged DNA binding activity of mtTFA through direct interaction. In: International Journal of Oncology. 2009 ; Vol. 35, No. 6. pp. 1435-1440.
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