TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states

The elucidation of the mechanisms whereby the liver maintains glucose homeostasis is crucial for the understanding of physiological and pathological states. Here, we show a novel role of hepatic transcriptional co-activator with PDZ-binding motif (TAZ) in the inhibition of glucocorticoid receptor (G...

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Autores principales:	Simiao Xu, Yangyang Liu, Ruixiang Hu, Min Wang, Oliver Stöhr, Yibo Xiong, Liang Chen, Hong Kang, Lingyun Zheng, Songjie Cai, Li He, Cunchuan Wang, Kyle D Copps, Morris F White, Ji Miao
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	hippo pathway effector transcriptional co-activator with PDZ-binding motif hepatic gluconeogenesis glucocorticoid receptor fasting and feeding Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/7eb4adb4d92c49ffb5a35b4e5dddc79d
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spelling	oai:doaj.org-article:7eb4adb4d92c49ffb5a35b4e5dddc79d2021-11-09T13:03:16ZTAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states10.7554/eLife.574622050-084Xe57462https://doaj.org/article/7eb4adb4d92c49ffb5a35b4e5dddc79d2021-10-01T00:00:00Zhttps://elifesciences.org/articles/57462https://doaj.org/toc/2050-084XThe elucidation of the mechanisms whereby the liver maintains glucose homeostasis is crucial for the understanding of physiological and pathological states. Here, we show a novel role of hepatic transcriptional co-activator with PDZ-binding motif (TAZ) in the inhibition of glucocorticoid receptor (GR). TAZ is abundantly expressed in pericentral hepatocytes and its expression is markedly reduced by fasting. TAZ interacts via its WW domain with the ligand-binding domain of GR to limit the binding of GR to the GR response element in gluconeogenic gene promoters. Therefore, liver-specific TAZ knockout mice show increases in glucose production and blood glucose concentration. Conversely, the overexpression of TAZ in mouse liver reduces the binding of GR to gluconeogenic gene promoters and glucose production. Thus, our findings demonstrate that hepatic TAZ inhibits GR transactivation of gluconeogenic genes and coordinates gluconeogenesis in response to physiological fasting and feeding.Simiao XuYangyang LiuRuixiang HuMin WangOliver StöhrYibo XiongLiang ChenHong KangLingyun ZhengSongjie CaiLi HeCunchuan WangKyle D CoppsMorris F WhiteJi MiaoeLife Sciences Publications Ltdarticlehippo pathway effectortranscriptional co-activator with PDZ-binding motifhepatic gluconeogenesisglucocorticoid receptorfasting and feedingMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hippo pathway effector transcriptional co-activator with PDZ-binding motif hepatic gluconeogenesis glucocorticoid receptor fasting and feeding Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	hippo pathway effector transcriptional co-activator with PDZ-binding motif hepatic gluconeogenesis glucocorticoid receptor fasting and feeding Medicine R Science Q Biology (General) QH301-705.5 Simiao Xu Yangyang Liu Ruixiang Hu Min Wang Oliver Stöhr Yibo Xiong Liang Chen Hong Kang Lingyun Zheng Songjie Cai Li He Cunchuan Wang Kyle D Copps Morris F White Ji Miao TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states
description	The elucidation of the mechanisms whereby the liver maintains glucose homeostasis is crucial for the understanding of physiological and pathological states. Here, we show a novel role of hepatic transcriptional co-activator with PDZ-binding motif (TAZ) in the inhibition of glucocorticoid receptor (GR). TAZ is abundantly expressed in pericentral hepatocytes and its expression is markedly reduced by fasting. TAZ interacts via its WW domain with the ligand-binding domain of GR to limit the binding of GR to the GR response element in gluconeogenic gene promoters. Therefore, liver-specific TAZ knockout mice show increases in glucose production and blood glucose concentration. Conversely, the overexpression of TAZ in mouse liver reduces the binding of GR to gluconeogenic gene promoters and glucose production. Thus, our findings demonstrate that hepatic TAZ inhibits GR transactivation of gluconeogenic genes and coordinates gluconeogenesis in response to physiological fasting and feeding.
format	article
author	Simiao Xu Yangyang Liu Ruixiang Hu Min Wang Oliver Stöhr Yibo Xiong Liang Chen Hong Kang Lingyun Zheng Songjie Cai Li He Cunchuan Wang Kyle D Copps Morris F White Ji Miao
author_facet	Simiao Xu Yangyang Liu Ruixiang Hu Min Wang Oliver Stöhr Yibo Xiong Liang Chen Hong Kang Lingyun Zheng Songjie Cai Li He Cunchuan Wang Kyle D Copps Morris F White Ji Miao
author_sort	Simiao Xu
title	TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states
title_short	TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states
title_full	TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states
title_fullStr	TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states
title_full_unstemmed	TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states
title_sort	taz inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/7eb4adb4d92c49ffb5a35b4e5dddc79d
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_version_	1718441029012553728

TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states

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