BCL3, AN I-KAPPA-B PROTEIN, AS A NOVEL TRANSCRIPTION COACTIVATOR OF THE RETINOID-X-RECEPTOR

We have recently shown that the I kappa B protein I kappa B beta inter acted with the retinoid X receptor (RXR) and inhibited the g-cis-retin oic acid (RA)-dependent transactivations (Na, S.-Y., Kim, H.-J,, Lee, S.-H., Choi, H.-S., Na, D. S., Lee, M.-O., Chung, M., Moore, D. D., an d Lee, J. W. (1998) J. Biol. Chem. 6, 3212-3215). Herein, we show that a distinct I kappa B protein Bcl3 also interacts with RXR, as shown i n the yeast two-hybrid tests and glutathione S-transferase pull-down a ssays. The Bcl3 interaction involved two distinct subregions of RXR, L e. constitutive interactions of the N-terminal ABC domains and 9-cis-R A-dependent interactions of the C-terminal DEF domains. In contrast to I kappa B beta, Bcl3 did not interact with the AF2 domain of RXR. Bcl 3 specifically interacted with the general transcription factors TFIIB , TBP, and TFIIA but not with TFIIE alpha in the GST pull-down assays. TBP and TFIIA,however, were not able to interact with I kappa B beta. Accordingly, Bcl3 coactivated the 9-cis-RA-induced transactivations o f RXR, in contrast to the inhibitory actions of I kappa B beta. In add ition, coexpression of SRC-1 but not p300 further stimulated the Bcl3- mediated enhancement of the g-cis-RA-induced transactivations of RXR. These results suggest that distinct I kappa B proteins differentially modulate the 9-cis-RA-induced transactivations of RXR in vivo.