ArticleThe Biochemical journal2007
Transcriptional repression of the gluconeogenic gene PEPCK by the orphan nuclear receptor SHP through inhibitory interaction with C/EBPalpha.
Article in The Biochemical journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- Bile Acids and Type 2 Diabetes: Roles in Glucose Homeostasis and Therapeutic Opportunities.Metabolites · 2025Review
- Bile Acid Signaling in Metabolic and Inflammatory Diseases and Drug Development.Pharmacological reviews · 2024Review
- Bile acid signaling in the regulation of whole body metabolic and immunological homeostasis.Science China. Life sciences · 2024Review
- Article
- Role of bile acids and their receptors in gastrointestinal and hepatic pathophysiology.Nature reviews. Gastroenterology & hepatology · 2022Review
- The long and the small collide: LncRNAs and small heterodimer partner (SHP) in liver disease.Molecular and cellular endocrinology · 2021Review
- T-Cell Death Associated Gene 51 Is a Novel Negative Regulator of PPARγ That Inhibits PPARγ-RXRα Heterodimer Formation in AdipogenesisMolecules and cells · 2021Article
- Metabolic Effects of Bile Acids: Potential Role in Bariatric Surgery.Cellular and molecular gastroenterology and hepatology · 2019Review
- Pharmacology of bile acid receptors: Evolution of bile acids from simple detergents to complex signaling molecules.Pharmacological research · 2016Review
- Nuclear Receptors as Therapeutic Targets in Liver Disease: Are We There Yet?Annual review of pharmacology and toxicology · 2016Review
- Modulation of the transcriptional activity of peroxisome proliferator-activated receptor gamma by protein-protein interactions and post-translational modifications.Yonsei medical journal · 2013Review
- A pleiotropic role for the orphan nuclear receptor small heterodimer partner in lipid homeostasis and metabolic pathways.Journal of lipids · 2012Article
- Bile Acid signaling in liver metabolism and diseases.Journal of lipids · 2012Article
- Role of nuclear receptor SHP in metabolism and cancer.Biochimica et biophysica acta · 2011Review
- Feedback regulation of hepatic gluconeogenesis through modulation of SHP/Nr0b2 gene expression by Sirt1 and FoxO1.American journal of physiology. Endocrinology and metabolism · 2011Article
- AMPK-dependent repression of hepatic gluconeogenesis via disruption of CREB.CRTC2 complex by orphan nuclear receptor small heterodimer partner.The Journal of biological chemistry · 2010Article
- Bile acids regulate hepatic gluconeogenic genes and farnesoid X receptor via G(alpha)i-protein-coupled receptors and the AKT pathway.Journal of lipid research · 2010Article
- Hepatitis B virus X protein impairs hepatic insulin signaling through degradation of IRS1 and induction of SOCS3.PloS one · 2010Article
- Bile acids as regulatory molecules.Journal of lipid research · 2009Review
- The orphan nuclear receptor SHP inhibits apoptosis during the monocytic differentiation by inducing p21WAF1.Experimental & molecular medicine · 2009Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SHP (short heterodimer partner) is an orphan nuclear receptor that plays an important role in regulating glucose and lipid metabolism. A variety of transcription factors are known to regulate transcription of the PEPCK (phosphoenolpyruvate carboxykinase) gene, which encodes a rate-determining enzyme in hepatic gluconeogenesis. Previous reports identified glucocorticoid receptor and Foxo1 as novel downstream targets regulating SHP inhibition [Borgius, Steffensen, Gustafsson and Treuter (2002) J. Biol. Chem. 277, 49761-49796; Yamagata, Daitoku, Shimamoto, Matsuzaki, Hirota, Ishida and Fukamizu (2004) J. Biol. Chem. 279, 23158-23165]. In the present paper, we show a new molecular mechanism of SHP-mediated inhibition of PEPCK transcription. We also show that the CRE1 (cAMP regulatory element 1; -99 to -76 bp relative to the transcription start site) of the PEPCK promoter is also required for the inhibitory regulation by SHP. SHP repressed C/EBPalpha (CCAAT/enhancer-binding protein alpha)-driven transcription of PEPCK through direct interaction with C/EBPalpha protein both in vitro and in vivo. The formation of an active transcriptional complex of C/EBPalpha and its binding to DNA was inhibited by SHP, resulting in the inhibition of PEPCK gene transcription. Taken together, these results suggest that SHP might regulate a level of hepatic gluconeogenesis driven by C/EBPalpha activation.
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