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Molecular and Cellular Biology, October 1998, p. 5880-5887, Vol. 18, No. 10
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Coactivator TIF1beta Interacts with Transcription Factor C/EBPbeta and Glucocorticoid Receptor To Induce alpha 1-Acid Glycoprotein Gene Expression

Ching-Jin Chang,1 Ya-Ling Chen,2,3 and Sheng-Chung Lee1,2,3,*

Institute of Biological Chemistry, Academia Sinica,1 and Institute of Molecular Medicine2 and H. L. Tsai Memorial Laboratory,3 College of Medicine, National Taiwan University, Taipei, Taiwan

Received 12 March 1998/Returned for modification 12 June 1998/Accepted 14 July 1998

The transcription of the alpha 1-acid glycoprotein gene is induced by inflammatory cytokines and glucocorticoids. C/EBPbeta 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, TIF1beta , which could enhance the transcription of the agp gene by the glucocorticoid receptor (GR) and C/EBPbeta . TIF1beta 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 TIF1beta is ligand independent. The overexpression of the TIF1beta gene enhances GR-regulated expression in a ligand- and glucocorticoid-responsive element (GRE)-dependent manner. TIF1beta can also augment C/EBPbeta -mediated activity on wild-type and GRE-mutated agp genes, but this augmentation is diminished when all three C/EBPbeta -binding elements are mutated. Functional and biochemical characterizations indicated that the bZIP domain of C/EBPbeta and the RBCC domain, plant homeodomain finger, and bromodomain of TIF1beta are crucial for the interactions of these proteins. Taken together, these results suggest that TIF1beta serves as a converging mediator of signal transduction pathways of glucocorticoids and some inflammatory cytokines.

* Corresponding author. Mailing address: Institute of Molecular Medicine, College of Medicine, National Taiwan University, #7 Chun Shan South Rd., Taipei, Taiwan. Phone: 886-2-2356-2982. Fax: 886-2-2321-0977. E-mail: slee{at}ccms.ntu.edu.tw.

Molecular and Cellular Biology, October 1998, p. 5880-5887, Vol. 18, No. 10
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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