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Liver X Receptor α Is Involved in the Transcriptional Regulation of the 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase Gene

The activity of 6-phosphofructo-1-kinase is strictly controlled by fructose-2,6-bisphosphate, the level of which is regulated by another enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK2/FBP2). PFK2/FBP2 is a bifunctional enzyme, having kinase and phosphatase activities, and regulat...

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Autores principales: Zhao, Li-Feng, Iwasaki, Yasumasa, Nishiyama, Mitsuru, Taguchi, Takafumi, Tsugita, Makoto, Okazaki, Mizuho, Nakayama, Shuichi, Kambayashi, Machiko, Fujimoto, Shimpei, Hashimoto, Koshi, Murao, Koji, Terada, Yoshio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3331782/
https://www.ncbi.nlm.nih.gov/pubmed/22415873
http://dx.doi.org/10.2337/db11-1255
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author Zhao, Li-Feng
Iwasaki, Yasumasa
Nishiyama, Mitsuru
Taguchi, Takafumi
Tsugita, Makoto
Okazaki, Mizuho
Nakayama, Shuichi
Kambayashi, Machiko
Fujimoto, Shimpei
Hashimoto, Koshi
Murao, Koji
Terada, Yoshio
author_facet Zhao, Li-Feng
Iwasaki, Yasumasa
Nishiyama, Mitsuru
Taguchi, Takafumi
Tsugita, Makoto
Okazaki, Mizuho
Nakayama, Shuichi
Kambayashi, Machiko
Fujimoto, Shimpei
Hashimoto, Koshi
Murao, Koji
Terada, Yoshio
author_sort Zhao, Li-Feng
collection PubMed
description The activity of 6-phosphofructo-1-kinase is strictly controlled by fructose-2,6-bisphosphate, the level of which is regulated by another enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK2/FBP2). PFK2/FBP2 is a bifunctional enzyme, having kinase and phosphatase activities, and regulates both glycolysis and gluconeogenesis. Here, we examined the hormonal regulation of the PFK2/FBP2 gene in vitro using the reporter assay, the electromobility shift assay (EMSA), and the chromatin immunoprecipitation (ChIP) assay in HuH7 cells and also using the mouse liver in vivo. We found that the transcriptional activity of the PFK2/FBP2 gene was stimulated by insulin and inhibited by cAMP and glucocorticoid. Liver X receptor (LXR) α showed a potent and specific stimulatory effect on PFK2/FBP2 gene transcription. Deletion and mutagenesis analyses identified the LXR response element (LXRE) in the 5′-promoter region of the PFK2/FBP2 gene. Binding of LXRα was confirmed by the EMSA and ChIP assay. Endogenous PFK2/FBP2 mRNA in the mouse liver was increased in the fasting/refeeding state compared with the fasting state. Altogether, PFK2/FBP2 gene transcription is found to be regulated in a way that is more similar to other glycolytic enzyme genes than to gluconeogenic genes. Furthermore, our data strongly suggest that LXRα is one of the key regulators of PFK2/FBP2 gene transcription.
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spelling pubmed-33317822013-05-01 Liver X Receptor α Is Involved in the Transcriptional Regulation of the 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase Gene Zhao, Li-Feng Iwasaki, Yasumasa Nishiyama, Mitsuru Taguchi, Takafumi Tsugita, Makoto Okazaki, Mizuho Nakayama, Shuichi Kambayashi, Machiko Fujimoto, Shimpei Hashimoto, Koshi Murao, Koji Terada, Yoshio Diabetes Metabolism The activity of 6-phosphofructo-1-kinase is strictly controlled by fructose-2,6-bisphosphate, the level of which is regulated by another enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK2/FBP2). PFK2/FBP2 is a bifunctional enzyme, having kinase and phosphatase activities, and regulates both glycolysis and gluconeogenesis. Here, we examined the hormonal regulation of the PFK2/FBP2 gene in vitro using the reporter assay, the electromobility shift assay (EMSA), and the chromatin immunoprecipitation (ChIP) assay in HuH7 cells and also using the mouse liver in vivo. We found that the transcriptional activity of the PFK2/FBP2 gene was stimulated by insulin and inhibited by cAMP and glucocorticoid. Liver X receptor (LXR) α showed a potent and specific stimulatory effect on PFK2/FBP2 gene transcription. Deletion and mutagenesis analyses identified the LXR response element (LXRE) in the 5′-promoter region of the PFK2/FBP2 gene. Binding of LXRα was confirmed by the EMSA and ChIP assay. Endogenous PFK2/FBP2 mRNA in the mouse liver was increased in the fasting/refeeding state compared with the fasting state. Altogether, PFK2/FBP2 gene transcription is found to be regulated in a way that is more similar to other glycolytic enzyme genes than to gluconeogenic genes. Furthermore, our data strongly suggest that LXRα is one of the key regulators of PFK2/FBP2 gene transcription. American Diabetes Association 2012-05 2012-04-13 /pmc/articles/PMC3331782/ /pubmed/22415873 http://dx.doi.org/10.2337/db11-1255 Text en © 2012 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Metabolism
Zhao, Li-Feng
Iwasaki, Yasumasa
Nishiyama, Mitsuru
Taguchi, Takafumi
Tsugita, Makoto
Okazaki, Mizuho
Nakayama, Shuichi
Kambayashi, Machiko
Fujimoto, Shimpei
Hashimoto, Koshi
Murao, Koji
Terada, Yoshio
Liver X Receptor α Is Involved in the Transcriptional Regulation of the 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase Gene
title Liver X Receptor α Is Involved in the Transcriptional Regulation of the 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase Gene
title_full Liver X Receptor α Is Involved in the Transcriptional Regulation of the 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase Gene
title_fullStr Liver X Receptor α Is Involved in the Transcriptional Regulation of the 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase Gene
title_full_unstemmed Liver X Receptor α Is Involved in the Transcriptional Regulation of the 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase Gene
title_short Liver X Receptor α Is Involved in the Transcriptional Regulation of the 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase Gene
title_sort liver x receptor α is involved in the transcriptional regulation of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene
topic Metabolism
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3331782/
https://www.ncbi.nlm.nih.gov/pubmed/22415873
http://dx.doi.org/10.2337/db11-1255
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