Back to Search
Start Over
Activation of TR4 orphan nuclear receptor gene promoter by cAMP/PKA and C/EBP signaling.
- Source :
-
Endocrine [Endocrine] 2009 Oct; Vol. 36 (2), pp. 211-7. Date of Electronic Publication: 2009 Jul 18. - Publication Year :
- 2009
-
Abstract
- In earlier studies, we had suggested that the fasting signal induces TR4 orphan nuclear receptor expression in vivo. The detailed mechanism(s), however, remain unclear. In this study, we found that cAMP/PKA, the mediator of fasting and glucagon signals, could induce TR4 gene expression that in turn modulates gluconeogenesis. Mechanistic dissection by in vitro studies in hepatocytes demonstrated that cAMP/PKA might trigger C/EBP alpha and beta binding to the selective cAMP response element, which is located at the TR4 promoter, thus inducing TR4 transcription. We also demonstrated that the binding activity of C/EBPs to the TR4 promoter is increased in response to cAMP treatment. Together, our data identified a new signaling pathway from the fasting signal --> cAMP/PKA --> C/EBP alpha and beta --> TR4 --> gluconeogenesis in hepatocytes; and suggested that TR4 could be an important regulator to control glucose homeostasis. The identification of activator(s)/inhibitor(s) or ligand(s) of TR4 may provide us an alternative way to control gluconeogenesis.
- Subjects :
- CCAAT-Enhancer-Binding Proteins metabolism
Cells, Cultured
Cyclic AMP physiology
Gene Expression Regulation
Gluconeogenesis genetics
Hepatocytes metabolism
Humans
Models, Biological
Protein Binding physiology
Protein Serine-Threonine Kinases genetics
Protein Serine-Threonine Kinases metabolism
RNA, Messenger genetics
RNA, Messenger metabolism
Receptors, Steroid metabolism
Receptors, Thyroid Hormone metabolism
Signal Transduction genetics
Signal Transduction physiology
CCAAT-Enhancer-Binding Proteins physiology
Cyclic AMP pharmacology
Cyclic AMP-Dependent Protein Kinases physiology
Promoter Regions, Genetic drug effects
Receptors, Steroid genetics
Receptors, Thyroid Hormone genetics
Transcriptional Activation drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1559-0100
- Volume :
- 36
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Endocrine
- Publication Type :
- Academic Journal
- Accession number :
- 19618297
- Full Text :
- https://doi.org/10.1007/s12020-009-9220-0