| Research Abstract |
Oxidative stresses such as ultraviolet (UV) irradiation to mammalian cells triggers variety of oxystress responses including activation of transcription factors. Recently, activation of nuclear factor-kappa B (NF-kappaB) has been shown to be under oxido-reduction (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 in vitro diamide-induced crosslinking 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 to 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 block 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 NP-kappaB complex, may be a novel activation mechanism of redox-sensitive transcription factors.
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