Cooperative regulation of endogenous cAMP-response element binding protein and CCAAT/enhancer-binding protein beta in GH-stimulated c-fos expression

The Journal of Endocrinology
Tracy Xiao CuiJessica Schwartz

Abstract

GH activates the c-fos promoter by regulating multiple transcription factors. This study adds to our understanding of GH-regulated transcription by demonstrating that GH regulates the c-fos cAMP-response element (CRE) and its binding protein, CREB. Activation of the c-fos promoter by GH is impaired by expression of dominant-negative A-CREB. GH stimulates rapid and transient phosphorylation of CREB at Ser 133 (P-CREB), a critical site for transactivation by CREB, in 3T3-F442A preadipocytes. Mutation of this residue impairs GH-induced c-fos expression, suggesting that phosphorylation of CREB at Ser 133 contributes to GH-induced c-fos activation. The MEK inhibitor UO126 impaired the phosphorylation of CREB and that of C/EBPbeta, suggesting that ERKs mediate the phosphorylation of both proteins. UO126, but not the protein kinase A inhibitor H89, blocked GH-induced c-fos mRNA expression. A combination of CREB and C/EBPbeta enhanced c-fos promoter activation, and mutation of the CRE impaired the enhancement, as well as GH-stimulated c-fos activation. GH treatment increased the occupancy of both endogenous phospho-CREB and phospho-C/EBPbeta on the c-fos promoter. The increases were impaired by UO126. The active P-CREB and P-C/EBPbeta ...Continue Reading

Citations

Feb 5, 2011·Molecular Endocrinology·Tracy X CuiJessica Schwartz
Jul 23, 2009·The Journal of Clinical Endocrinology and Metabolism·Maria Chiara ZatelliEttore degli Uberti
Jan 6, 2016·Journal of Cellular Biochemistry·Alejandro MaureiraJosé L Gutiérrez

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