Distinct Roles of Thioredoxin in the Cytoplasm and in the Nucleus

作者：Kiichi Hirota, Miyahiko Murata, Yoshifumi Sachi, Hajime Nakamura, Junko S. Takeuchi, Kenjiro Mori, Junji Yodoi · 发表于：Journal of Biological Chemistry · 年份：1999 · DOI：10.1074/jbc.274.39.27891 · 被引用次数：612 · 研究领域：Redox biology and oxidative stress、Genomics, phytochemicals, and oxidative stress、Glutathione Transferases and Polymorphisms

Oxidative stresses such as UV irradiation to mammalian cells triggers a variety of oxistress responses including activation of transcription factors. Recently, activation of nuclear factor-kappaB (NF-kappaB) has been shown to be under oxidoreduction (redox) regulation controlled by thioredoxin (TRX), which is one of major endogenous redox-regulating molecules with thiol reducing activity. In order to elucidate where in the cellular compartment TRX participates in NF-kappaB regulation, we investigated the intracellular localization of TRX. UVB irradiation induced translocation of TRX from the cytoplasm into the nucleus. In our in vitro diamide-induced cross-linking study, we showed that TRX can associate directly with NF-kappaB p50. Overexpression of wild-type TRX suppressed induction of luciferase activity under NF-kappaB-binding sites in response to UV irradiation compared with the mock transfectant. In contrast, overexpression of nuclear-targeted TRX enhanced the luciferase activity. Thus, TRX seems to play dual and opposing roles in the regulation of NF-kappaB. In the cytoplasm, it interferes with the signals to IkappaB kinases and blocks the degradation of IkappaB. In the nucleus, however, TRX enhances NF-kappaB transcriptional activities by enhancing its ability to bind DNA. This two-step TRX-dependent regulation of the NF-kappaB complex may be a novel activation mechanism of redox-sensitive transcription factors.