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; Jesang Ko

doi:10.1016/j.bbrc.2018.05.077

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, Jesang Ko

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

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 language	English
Pages (from-to)	800-806
Number of pages	7
Journal	Biochemical and biophysical research communications
Volume	501
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2018.05.077
Publication status	Published - 2018 Jun 27

Bibliographical note

Funding Information:
This work was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C1906) and the Korea University Grant.

Funding Information:
This work was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C1906 ) and the Korea University Grant.

Publisher Copyright:
© 2018 Elsevier Inc.

Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.

Keywords

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

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2018.05.077

Cite this

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

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.",

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author = "Yunhee Hwang and An, {Hyoung Tae} and Minsoo Kang and Jesang Ko",

note = "Funding Information: This work was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C1906) and the Korea University Grant. Funding Information: This work was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C1906 ) and the Korea University Grant. Publisher Copyright: {\textcopyright} 2018 Elsevier Inc. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",

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AU - Hwang, Yunhee

AU - An, Hyoung Tae

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AU - Ko, Jesang

N1 - Funding Information: This work was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C1906) and the Korea University Grant. Funding Information: This work was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C1906 ) and the Korea University Grant. Publisher Copyright: © 2018 Elsevier Inc. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.

PY - 2018/6/27

Y1 - 2018/6/27

N2 - 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.

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

Abstract

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Keywords

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