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Thioredoxin-2 (TRX-2) is an essential gene regulating mitochondria-dependent apoptosis

Tanaka, Toru (author)
Department of Biological Responses, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan
Hosoi, Fumihito (author)
Department of Biological Responses, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan
Yamaguchi-Iwai, Yuko (author)
Department of Applied Molecular Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, Japan
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Nakamura, Hajime (author)
Department of Biological Responses, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan
Masutani, Hiroshi (author)
Department of Biological Responses, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan
Ueda, Shugo (author)
Department of Biological Responses, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan
Nishiyama, Akira (author)
Department of Biological Responses, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan
Takeda, Shunichi (author)
Department of Experimental Radiology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan
Wada, Hiromi (author)
Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto Japan
Spyrou, Giannis (author)
Department of Biosciences at Novum, Karolinska Institutet, Huddinge, Sweden
Yodoi, Junji (author)
Department of Biological Responses, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto / Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology, Ikeda, Osaka , Japan
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 (creator_code:org_t)
Wiley-Blackwell, 2002
2002
English.
In: EMBO Journal. - : Wiley-Blackwell. - 0261-4189 .- 1460-2075. ; 21:7, s. 1695-703
Related links:
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Thioredoxin-2 (Trx-2) is a mitochondria-specific member of the thioredoxin superfamily. Mitochondria have a crucial role in the signal transduction for apoptosis. To investigate the biological significance of Trx-2, we cloned chicken TRX-2 cDNA and generated clones of the conditional Trx-2-deficient cells using chicken B-cell line, DT40. Here we show that TRX-2 is an essential gene and that Trx-2-deficient cells undergo apoptosis upon repression of the TRX-2 transgene, showing an accumulation of intracellular reactive oxygen species (ROS). Cytochrome c is released from mitochondria, while caspase-9 and caspase-3, but not caspase-8, are activated upon inhibition of the TRX-2 transgene. In addition, Trx-2 and cytochrome c are co-immunoprecipitated in an in vitro assay. These results suggest that mitochondrial Trx-2 is essential for cell viability, playing a crucial role in the scavenging ROS in mitochondria and regulating the mitochondrial apoptosis signaling pathway.

Keyword

apoptosis
cytochrome
mitochondria
redox
thioredoxin-2

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