NEGATIVE INTERACTION BETWEEN THE RELA(P65) SUBUNIT OF NF-KAPPA-B AND THE PROGESTERONE-RECEPTOR

Interactions between transcription factors are am important means of r egulating gene transcription. The present study describes the mutual r epression of two transcription factors, the RelA(p65) subunit of NF-ka ppa B and the progesterone receptor (PR). This trans-repression is sho wn to occur independent of PR isoform, reporter construct, or cell typ e used. Together with the demonstration of an interaction between PR a nd RelA in vitro, these findings suggest that the mutual repression is due to a direct interaction between these proteins. Furthermore, acti vation of NF-kappa B by tumor necrosis factor-alpha also results in re pression of PR, while PR is able to repress tumor necrosis factor-alph a-induced NF-kappa B activity. Since NF-kappa B-regulating cytokine re ceptors are expressed in progesterone target tissues, like breast and endometrium, the mutual repression of PR and RelA could play an import ant role in a wide variety of physiological processes in these tissues , including maintenance of pregnancy, immunosuppression, and tumorigen esis.