C/EBPβ Mediates Growth Hormone-Regulated Expression of Multiple Target Genes

Abstract

Regulation of c-Fos transcription by GH is mediated by CCAAT/enhancer binding protein β (C/EBPβ). This study examines the role of C/EBPβ in mediating GH activation of other early response genes, including Cyr61, Btg2, Socs3, Zfp36, and Socs1. C/EBPβ depletion using short hairpin RNA impaired responsiveness of these genes to GH, as seen for c-Fos. Rescue with wild-type C/EBPβ led to GH-dependent recruitment of the coactivator p300 to the c-Fos promoter. In contrast, rescue with C/EBPβ mutated at the ERK phosphorylation site at T188 failed to induce GH-dependent recruitment of p300, indicating that ERK-mediated phosphorylation of C/EBPβ at T188 is required for GH-induced recruitment of p300 to c-Fos. GH also induced the occupancy of phosphorylated C/EBPβ and p300 on Cyr61, Btg2, and Socs3 at predicted C/EBP-cAMP response element-binding protein motifs in their promoters. Consistent with a role for ERKs in GH-induced expression of these genes, treatment with U0126 to block ERK phosphorylation inhibited their GH-induced expression. In contrast, GH-dependent expression of Zfp36 and Socs1 was not inhibited by U0126. Thus, induction of multiple early response genes by GH in 3T3-F442A cells is mediated by C/EBPβ. A subset of these genes is regulated similarly to c-Fos, through a mechanism involving GH-stimulated ERK 1/2 activation, phosphorylation of C/EBPβ, and recruitment of p300. Overall, these studies suggest that C/EBPβ, like the signal transducer and activator of transcription proteins, regulates multiple genes in response to GH.

B-cell translocation gene 2 positively regulates GLP-1-stimulated insulin secretion via induction of PDX-1 in pancreatic β-cells

“…22 Moreover, Cui et al 30 showed that growth hormone, which is a stimulator of hepatic gluconeogenesis, significantly increases BTG2 via the C/EBP-CREB pathway in adipocytes, suggesting that BTG2 may be involved in hepatic gluconeogenesis, consistent with a previous report. A recent report suggests that liraglutide, a GLP-1 agonist, increases the ATP/AMP ratio, which in turn inhibits AMP-activated protein kinase.…”

Increased serum human β-defensin-2 levels in atopic dermatitis: Relationship to IL-22 and oncostatin M

“…hBD-2-induced ERK or JNK might promote IL-22 or oncostatin M production, respectively. It is reported that ERK activates Sp1 and C/EBP by inducing their phosphorylation and/or expression (Chanteux et al 2007;Cui et al 2011;Lue et al 2011), while JNK activates AP-1 via phosphorylation and/or expression of AP-1 components like c-Jun (Lue et al 2011). Thus, hBD-2-induced ERK or JNK could activate Sp1/C/EBP or AP-1 to promote IL-22 or oncostatin M expression, respectively.…”

CCN1/CYR61: the very model of a modern matricellular protein

“…Exquisitely sensitive to a wide range of extracellular stimuli, CCN1 is transcriptionally activated by platelet-derived growth factor and fibroblast growth factor 2 [8], transforming growth factor β1 (TGF-β1) [19], growth hormone [20], the phorbol ester 12- O -tetradecanoylphorbol-13-acetate, cAMP [8], vitamin D 3 [21], estrogen and tamoxifen [22], angiotensin II [23,24], hypoxia [25], UV light [26], and mechanical stretch [27,28]. Consistent with a role in inflammation, CCN1 is also induced by bacterial and viral infections [29–32], and by inflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor α (TNF-α) [33].…”