Roles of 14-3-3β and γ in regulation of the glucocorticoid receptor transcriptional activation and hepatic gluconeogenesis

Journal Article · Fri Jun 15 04:00:00 EDT 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.05.077· OSTI ID:23125073

Hwang, Yunhee; An, Hyoung-Tae; Kang, Minsoo; Ko, Jesang ^[1]

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1. Division of Life Sciences, Korea University, Seoul, 02841, South (Korea, Republic of)

The glucocorticoid receptor (GR) is a ligand-dependent transcription factor that mediates the effects of glucocorticoids, and plays a crucial role in cell growth, development, inflammation, and gluconeogenesis. The 14-3-3 proteins bind to target proteins via phosphorylation, and influence many cellular events by altering their subcellular localization or by acting as chaperones. However, the mechanisms by which 14-3-3 proteins regulate GR transactivation and their involvement in gluconeogenesis remain uncharacterized. We found that 14-3-3β and γ increased GR transcriptional activity and the promoter activities of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase in the presence of glucocorticoids. Inhibition of the endogenous 14-3-3β and γ decreased dexamethasone- and cAMP-stimulated PEPCK expression. Further, both 14-3-3β and γ increased glucose production in response to glucocorticoids. Our findings suggest that 14-3-3β and γ function as positive regulators of GR transactivation and glucocorticoid-mediated hepatic gluconeogenesis.

• OSTI ID: 23125073
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 501; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
DEXAMETHASONE
GLUCOSE
INFLAMMATION
LIVER
PHOSPHATASES
PHOSPHOENOLPYRUVATE
PHOSPHORYLATION