Molecular targeting of nuclear transcriptional regulators

Gene regulation by nuclear transcription factors involves intracellular interactions of nuclear transcriptors with specific transport carriers and/or DNA regulatory elements using sequence-specific recognition sites. In this study, we utilized a series of synthetic peptides carrying the nuclear localization sequence of the transcriptor NF-κB p50 and p65 subunits to inhibit NF-κB-mediated gene expression. Gene transfection and gel-shift assays showed that these peptides were effective in inhibiting the nuclear translocation and transcriptional activation of NF-κB. However, their effects required the presence of a cell-permeable peptide which is covalently linked to the inhibitory peptides. These hybrid peptides may be used as novel therapeutic agents in diseases whose etiology is dependent on NF-κB activation.