Cargando…
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...
Autores principales: | , , , , , , , , , , , |
---|---|
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 |
_version_ | 1782230144019070976 |
---|---|
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. |
format | Online Article Text |
id | pubmed-3331782 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT zhaolifeng liverxreceptoraisinvolvedinthetranscriptionalregulationofthe6phosphofructo2kinasefructose26bisphosphatasegene AT iwasakiyasumasa liverxreceptoraisinvolvedinthetranscriptionalregulationofthe6phosphofructo2kinasefructose26bisphosphatasegene AT nishiyamamitsuru liverxreceptoraisinvolvedinthetranscriptionalregulationofthe6phosphofructo2kinasefructose26bisphosphatasegene AT taguchitakafumi liverxreceptoraisinvolvedinthetranscriptionalregulationofthe6phosphofructo2kinasefructose26bisphosphatasegene AT tsugitamakoto liverxreceptoraisinvolvedinthetranscriptionalregulationofthe6phosphofructo2kinasefructose26bisphosphatasegene AT okazakimizuho liverxreceptoraisinvolvedinthetranscriptionalregulationofthe6phosphofructo2kinasefructose26bisphosphatasegene AT nakayamashuichi liverxreceptoraisinvolvedinthetranscriptionalregulationofthe6phosphofructo2kinasefructose26bisphosphatasegene AT kambayashimachiko liverxreceptoraisinvolvedinthetranscriptionalregulationofthe6phosphofructo2kinasefructose26bisphosphatasegene AT fujimotoshimpei liverxreceptoraisinvolvedinthetranscriptionalregulationofthe6phosphofructo2kinasefructose26bisphosphatasegene AT hashimotokoshi liverxreceptoraisinvolvedinthetranscriptionalregulationofthe6phosphofructo2kinasefructose26bisphosphatasegene AT muraokoji liverxreceptoraisinvolvedinthetranscriptionalregulationofthe6phosphofructo2kinasefructose26bisphosphatasegene AT teradayoshio liverxreceptoraisinvolvedinthetranscriptionalregulationofthe6phosphofructo2kinasefructose26bisphosphatasegene |