Artículos de revistas
C/EBP beta mediates growth hormone-regulated expression of multiple target genes
Fecha
2011-04Registro en:
Cui, Tracy X.; Lin, Grace; Lapensee, Christopher R.; Calinescu, Anda Alexandra; Rathore, Maanjot; et al.; C/EBP beta mediates growth hormone-regulated expression of multiple target genes; Endocrine Society; Molecular Endocrinology; 25; 4; 4-2011; 681-693
0888-8809
1944-9917
Autor
Cui, Tracy X.
Lin, Grace
Lapensee, Christopher R.
Calinescu, Anda Alexandra
Rathore, Maanjot
Streeter, Cale
Piwien Pilipuk, Graciela
Lanning, Nathan
Jin, Hui
Carter Su, Christin
Qin, Zhaohui S.
Schwartz, Jessica
Resumen
Regulation of c-Fos transcription by GH is mediated by CCAAT/enhancer binding protein (C/ EBP ). This study examines the role of C/EBP in mediating GH activation of other early response genes, including Cyr61, Btg2, Socs3, Zfp36, and Socs1. C/EBP depletion using short hairpin RNA impaired responsiveness of these genes to GH, as seen for c-Fos. Rescue with wild-type C/EBP led to GH-dependent recruitment of the coactivator p300 to the c-Fos promoter. In contrast, rescue with C/EBP mutated at the ERK phosphorylation site at T188 failed to induce GH-dependent recruitment of p300, indicating that ERK-mediated phosphorylation of C/EBP at T188 is required for GH-induced recruitment of p300 to c-Fos. GH also induced the occupancy of phosphorylated C/EBP 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/EBP . A subset of these genes is regulated similarly to c-Fos, through a mechanism involving GH-stimulated ERK 1/2 activation, phosphorylation of C/EBP , and recruitment of p300. Overall, these studies suggest that C/EBP , like the signal transducer and activator of transcription proteins, regulates multiple genes in response to GH.