Coactivator TTF1β interacts with transcription factor C EBPβ and gluco-corticoid receptor to induce α1-acid glycoprotein gene expression

The transcription of the alpha 1-acid glycoprotein gene is induced by inflammatory cytokines and glucocorticoids. C/EBP beta is a major transcription factor involved in the induction of the agp gene by some cytokines. In this report, we have identified a novel transcriptional intermediary factor, TIF1 beta, which could enhance the transcription of the agp gene by the glucocorticoid receptor (GR) and C/EBP beta. TIF1 beta belongs to re subgroup of RING (really interesting new gene) finger proteins that contain a RING finger preceding two B hox-type fingers and a putative coiled-coil domain (RBCC domain). Immunoprecipitation experiments showed that the interaction between GR and TIF1 beta is ligand independent. The overexpression of the TIF1 beta gene enhances GR-regulated expression in a ligand- and glucocorticoid-responsive element (GRE)-dependent manner. TIF1 beta can also augment C/EBP beta-mediated activity on wild-type and GRE-mutated agp genes, but this augmentation is diminished when all three C/EBP beta-binding elements are mutated. Functional and biochemical characterizations indicated that the bZIP domain of C/EBP beta and the RBCC domain, plant homeodomain finger, and bromodomain of TIF1 beta are crucial for the interactions of these proteins. Taken together, these results suggest that TIF1 beta serves as a converging mediator of signal transduction pathways of glucocorticoids and same inflammatory cytokines.