Metallothionein (MT), a low molecular weight, cysteine-rich metal binding protein, has been associated with cytoprotection from heavy metals and cellular oxidants. As MT has the ability to scavenge hydroxyl radicals, MT may control intracellular redox status. In the present study, we examined whether MT regulates the activity of nuclear factor-U UB (NF-U UB), which is one of the redox-regulated transcription factors, using the MT null embryonic cell lines established from MT null mice. We first found that tumor necrosis factor (TNF)-induced activation of the binding of NF-U UB protein to DNA in wild type MT+/+ cells was lower than that in MT3 3/3 3 cells. The NF-U UB activation in MT-expressing cells established from MT3 3/3 3 cells by the transfection of mouse MT-I gene was also significantly lower than that in MT3 3/3 3 cells. In addition, transfection of the MT gene inhibited TNF-induced IU UB degradation and suppressed NF-U UB-dependent gene expression induced by TNF. These results demonstrate that MT may function as a negative regulator of NF-U UB activity.z 1999 Federation of European Biochemical Societies.

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