Coactivator TIF1beta interacts with transcription factor C/EBPbeta and glucocorticoid receptor to induce alpha1-acid glycoprotein gene expression.
The transcription of the alpha1-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.
Chang
C J
CJ
Institute of Biological Chemistry, Academia Sinica, College of Medicine, National Taiwan University, Taipei, Taiwan.
Chen
Y L
YL
Lee
S C
SC
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002460:Cell Line; D006224:Cricetinae; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D009961:Orosomucoid / Q000235:genetics*; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000076183:Tripartite Motif-Containing Protein 28
D022762:CCAAT-Enhancer-Binding Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D009961:Orosomucoid; D011965:Receptors, Glucocorticoid; D012097:Repressor Proteins; D014157:Transcription Factors; C101116:TRIM28 protein, human; C486304:Trim28 protein, rat; D000076183:Tripartite Motif-Containing Protein 28