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Distinct Roles of Thioredoxin in the Cytoplasm and in the Nucleus

K. Hirota,M. Murata,Y. Sachi,Hajime Nakamura,J. Takeuchi,K. Mori,J. Yodoi

Published 1999 in Journal of Biological Chemistry

ABSTRACT

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-κB (NF-κB) 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-κB 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-κB p50. Overexpression of wild-type TRX suppressed induction of luciferase activity under NF-κB-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-κB. In the cytoplasm, it interferes with the signals to IκB kinases and blocks the degradation of IκB. In the nucleus, however, TRX enhances NF-κB transcriptional activities by enhancing its ability to bind DNA. This two-step TRX-dependent regulation of the NF-κB complex may be a novel activation mechanism of redox-sensitive transcription factors.

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