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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555985/ https://www.ncbi.nlm.nih.gov/pubmed/34622775 http://dx.doi.org/10.7554/eLife.57462 |
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author | Xu, Simiao Liu, Yangyang Hu, Ruixiang Wang, Min Stöhr, Oliver Xiong, Yibo Chen, Liang Kang, Hong Zheng, Lingyun Cai, Songjie He, Li Wang, Cunchuan Copps, Kyle D White, Morris F Miao, Ji |
author_facet | Xu, Simiao Liu, Yangyang Hu, Ruixiang Wang, Min Stöhr, Oliver Xiong, Yibo Chen, Liang Kang, Hong Zheng, Lingyun Cai, Songjie He, Li Wang, Cunchuan Copps, Kyle D White, Morris F Miao, Ji |
author_sort | Xu, Simiao |
collection | PubMed |
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 | Online Article Text |
id | pubmed-8555985 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-85559852021-11-01 TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states Xu, Simiao Liu, Yangyang Hu, Ruixiang Wang, Min Stöhr, Oliver Xiong, Yibo Chen, Liang Kang, Hong Zheng, Lingyun Cai, Songjie He, Li Wang, Cunchuan Copps, Kyle D White, Morris F Miao, Ji eLife Biochemistry and Chemical Biology 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. eLife Sciences Publications, Ltd 2021-10-08 /pmc/articles/PMC8555985/ /pubmed/34622775 http://dx.doi.org/10.7554/eLife.57462 Text en © 2021, Xu et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Biochemistry and Chemical Biology Xu, Simiao Liu, Yangyang Hu, Ruixiang Wang, Min Stöhr, Oliver Xiong, Yibo Chen, Liang Kang, Hong Zheng, Lingyun Cai, Songjie He, Li Wang, Cunchuan Copps, Kyle D White, Morris F Miao, Ji TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states |
title | 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_short | 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 |
topic | Biochemistry and Chemical Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555985/ https://www.ncbi.nlm.nih.gov/pubmed/34622775 http://dx.doi.org/10.7554/eLife.57462 |
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