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

Abstract

The transcription of the ␣1-acid glycoprotein gene is induced by inflammatory cytokines and glucocorticoids. C/EBP␤ 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␤, which could enhance the transcription of the agp gene by the glucocorticoid receptor (GR) and C/EBP␤. TIF1␤ 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 TIF1␤ is ligand independent. The overexpression of the TIF1␤ gene enhances GR-regulated expression in a ligand-and glucocorticoid-responsive element (GRE)-dependent manner. TIF1␤ can also augment C/EBP␤-mediated activity on wild-type and GRE-mutated agp genes, but this augmentation is diminished when all three C/EBP␤-binding elements are mutated. Functional and biochemical characterizations indicated that the bZIP domain of C/EBP␤ and the RBCC domain, plant homeodomain finger, and bromodomain of TIF1␤ are crucial for the interactions of these proteins. Taken together, these results suggest that TIF1␤ serves as a converging mediator of signal transduction pathways of glucocorticoids and some inflammatory cytokines.

Identification of a Co-repressor That Inhibits the Transcriptional and Growth-Arrest Activities of CCAAT/Enhancer-binding Protein α

“…In the case of C/EBP␤, p300 appears to be a coactivator, based on its ability to enhance C/EBP␤-dependent transactivation and physically interact with multiple regions in the amino terminus of C/EBP␤ (15). TIF1␤ has also been demonstrated to be a co-activator of C/EBP␤ (42). However, this co-activator appears to interact with the bZIP domain of C/EBP␤.…”

Anti-inflammatory functions of glucocorticoid-induced genes

“…Least direct of all, GCs can upregulate expression of C/EBPs, for example in muscle (Penner et al, 2002;Yang et al, 2005), liver Gotoh et al, 1997;Matsuno et al, 1996;Ramos et al, 1996) or differentiating adipocytes (Hernandez et al, 2003;Shi et al, 2000). Secondly, GR can cooperate with C/EBP transcription factors to activate transcription through composite response elements such as those of α1 acid glycoprotein (Alam et al, 1993;Chang et al, 1998;Savoldi et al, 1997), PEPCK (Arizmendi et al, 1999;Crosson and Roesler, 2000;Yamada et al, 1999) and β casein genes (Wyszomierski and Rosen, 2001). Finally, GCs can enhance the function of C/EBPβ.…”

Autocrine/Paracrine Secreted Frizzled-related Protein 2 Induces Cellular Resistance to Apoptosis

“…For experiments with blocking antibody (integrin ␣ 5 ␤ 1 , 0.1 mg/ml) or soluble heparin (0.1 mg/ml, Sigma), cells were preincubated at 37°C for 30 min. The details of immunoprecipitation and immunoblotting were performed essentially as described previously (26). To avoid difficult extraction of insoluble FN by routine immunoprecipitation lysis buffer, the cells were preincubated with soluble FN (Invitrogen) for 1 h. Whole cell extracts were prepared by lysing the cells with buffer containing 25 mM HEPES (pH 7.6), 0.3 M NaCl, 1.5 mM MgCl 2 , 0.2 mM EDTA, 0.5% Nonidet P-40, and 0.5 mM dithiothreitol.…”