TY - JOUR
T1 - Thioredoxin2 enhances the damaged DNA binding activity of mtTFA through direct interaction
AU - Kidani, Akihiko
AU - Izumi, Hiroto
AU - Yoshida, Yoichiro
AU - Kashiwagi, Eiji
AU - Ohmori, Haruki
AU - Tanaka, Tsuneo
AU - Kuwano, Michihiko
AU - Kohno, Kimitoshi
PY - 2009/12/1
Y1 - 2009/12/1
N2 - 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.
AB - 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.
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U2 - 10.3892/ijo-00000462
DO - 10.3892/ijo-00000462
M3 - Article
C2 - 19885567
AN - SCOPUS:73949102427
VL - 35
SP - 1435
EP - 1440
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 6
ER -
