Negative Interaction Between the RelA(p65) Subunit of NF-kappaB and the Progesterone Receptor

Interactions between transcription factors are an important means of regulating gene transcription. The present study describes the mutual repression of two transcription factors, the RelA(p65) subunit of NF-kappaB and the progesterone receptor (PR). This trans-repression is shown to occur independent of PR isoform, reporter construct, or cell type used. Together with the demonstration of an interaction between PR and RelA in vitro, these findings suggest that the mutual repression is due to a direct interaction between these proteins. Furthermore, activation of NF-kappaB by tumor necrosis factor-alpha also results in repression of PR, while PR is able to repress tumor necrosis factor-alpha-induced NF-kappaB activity. Since NF-KB-regulating cytokine receptors are expressed in progesterone target tissues, like breast and endometrium, the mutual repression of PR and RelA could play an important role in a wide variety of physiological processes in these tissues, including maintenance of pregnancy, immunosuppression, and tumorigenesis.