DISTINCT DOMAINS OF THE RELA NF-KAPPA-B SUBUNIT ARE REQUIRED FOR NEGATIVE CROSS-TALK AND DIRECT INTERACTION WITH THE GLUCOCORTICOID RECEPTOR

The RelA subunit of NF-kappa B and the glucocorticoid receptor mutuall y repress each others transcriptional activity, thus providing a mecha nism for immunosuppression, Deletion analysis of the glucocorticoid re ceptor has shown that the DNA binding domain and the ligand binding do main are essential components for repression, Here, we show by deletio ns and point mutations that both the Rel homology domain and the trans activation domains of RelA are required for repression of the transcri ptional activity of the glucocorticoid receptor in intact cells, Howev er, only the Rel homology domain of RelA was found to associate with t he glucocorticoid receptor in vitro. RelA mutants, not able to repress glucocorticoid receptor activity, but still able to dimerize, behaved as transdominant inhibitors of the repressive activity of wild type R elA. Furthermore, we show that the 13 S E1A protein is able to interfe re with the transrepressive activity of RelA. We propose that negative cross-talk between the glucocorticoid receptor and RelA is due to dir ect interaction via the Rel homology domain of RelA and the DNA bindin g domain of the glucocorticoid receptor in combination with interferen ce by the transactivation domains of RelA with the transcriptional act ivity of the glucocorticoid receptor.