Coactivator TIF1β Interacts with Transcription Factor C/EBPβ and Glucocorticoid Receptor To Induce α1-Acid Glycoprotein Gene Expression

ABSTRACT

The transcription of the α1-acid glycoprotein gene is induced by inflammatory cytokines and glucocorticoids. C/EBPβ is a major transcription factor involved in the induction of the agpgene by some cytokines. In this report, we have identified a novel transcriptional intermediary factor, TIF1β, which could enhance the transcription of the agp gene by the glucocorticoid receptor (GR) and C/EBPβ. TIF1β belongs to a subgroup of RING (really interesting new gene) finger proteins that contain a RING finger preceding two B box-type fingers and a putative coiled-coil domain (RBCC domain). Immunoprecipitation experiments showed that the interaction between GR and TIF1β is ligand independent. The overexpression of the TIF1β gene enhances GR-regulated expression in a ligand- and glucocorticoid-responsive element (GRE)-dependent manner. TIF1β can also augment C/EBPβ-mediated activity on wild-type and GRE-mutated agp genes, but this augmentation is diminished when all three C/EBPβ-binding elements are mutated. Functional and biochemical characterizations indicated that the bZIP domain of C/EBPβ and the RBCC domain, plant homeodomain finger, and bromodomain of TIF1β are crucial for the interactions of these proteins. Taken together, these results suggest that TIF1β serves as a converging mediator of signal transduction pathways of glucocorticoids and some inflammatory cytokines.

ACKNOWLEDGMENTS

This research was supported by grants NSC86-2311-B001-089 and NSC88-2311-B001-114 (to C.-J.C.) and NSC86-2311-B001-094-Y (to S.-C.L.) from the National Science Council.

We thank Susan Taylor, Sophia Tasi, and Ming-Jer Tasi for plasmids and Bertrand Chin-Ming Tan for critical reading of the manuscript.