Nuclear factor loB (NF-IcB) is a transcription factor that is critical for the inducible expression of multiple cellular and viral genes. DNA binding activity is essential for its function. Here, we report that gold compounds, especially aurothioglucose (AuTG), have a strong inhibitory effect on NF-JcB-DNA binding. Our finding also reveals that Zn 2÷ is a necessary component of NF-JcB for its DNA binding activity and that gold ion can efficiently block NF-~,--DNA binding, presumably through oxidation of the cysteins associated with zinc. This redox mechanism may provide an explanation for the observed efficacy of gold compounds in the treatment of rheumatoid arthritis.

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Gene expression of human immunodeficiency virus (HIV) depends on a host cellular transcription factors including nuclear factor-gB (NF-~B

Since the recognition of its pivotal role in viral replication, Tat activity has become an interesting target for chemotherapeutic intervention of HIV infection. Here, we report a sensitive and simple colorimetric assay for the screening of Tat inhibitors. We have constructed a plasmid that contains the hygromycin B phosphotransferase gene under the control of the HIV-1 long terminal repeat (LTR) and HIV-1 tat gene constitutively expressed from the cytomegalovirus promoter. This plasmid has been stably transfected to the CD4+ T cell line CEM, which is rendered resistant to hygromycin B through the action of Tat. The inhibitory activity of the anti-Tat drugs was assessed by the extent of cytotoxicity in the presence of hygromycin B as a consequence of the suppressed expression of the hygromycin B phosphotransferase gene. Spectrophotometric quantitation of cell viability was done utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) dye as the indicator. Using this assay system, we have confirmed that known anti-Tat compound Ro5-3335 and its derivative Ro24-7429 could inhibit Tat-mediated gene expression although their selectivities (anti-Tat activity versus nonselective cytotoxicity) were narrow. Since this method offers the advantage of not handling infectious particles or radioactive materials, it can offer wide applicability as a screening system for anti-Tat compounds.