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

Yunhee Hwang, Hyoung Tae An, Minsoo Kang, Je Sang Ko

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)800-806
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume501
Issue number3
DOIs
Publication statusPublished - 2018 Jun 27

Fingerprint

Gluconeogenesis
Glucocorticoid Receptors
Transcriptional Activation
Glucocorticoids
Chemical activation
14-3-3 Proteins
Phosphoenolpyruvate
Liver
Glucose-6-Phosphatase
Phosphorylation
Cell growth
Growth and Development
Dexamethasone
Transcription Factors
Ligands
Inflammation
Glucose
Proteins

Keywords

  • 14-3-3
  • Glucocorticoid receptor
  • Gluconeogenesis
  • Glucose-6-phosphatase
  • Phosphoenolpyruvate carboxykinase

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Roles of 14-3-3β and γ in regulation of the glucocorticoid receptor transcriptional activation and hepatic gluconeogenesis. / Hwang, Yunhee; An, Hyoung Tae; Kang, Minsoo; Ko, Je Sang.

In: Biochemical and Biophysical Research Communications, Vol. 501, No. 3, 27.06.2018, p. 800-806.

Research output: Contribution to journalArticle

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