Functional interplay between the transcription factors USF1 and PDX-1 and protein kinase CK2 in pancreatic β-cells

Abstract Glucose homeostasis is regulated by insulin, which is produced in the β-cells of the pancreas. The synthesis of insulin is controlled by several transcription factors including PDX-1, USF1 and USF2. Both, PDX-1 and USF1 were identified as substrates for protein kinase CK2. Here, we have ana...

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Autores principales:	Sarah Spohrer, Rebecca Groß, Lisa Nalbach, Lisa Schwind, Heike Stumpf, Michael D. Menger, Emmanuel Ampofo, Mathias Montenarh, Claudia Götz
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2ec05ada4cd64bb4ab2b9b3d3a635f8d
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spelling	oai:doaj.org-article:2ec05ada4cd64bb4ab2b9b3d3a635f8d2021-12-02T15:06:05ZFunctional interplay between the transcription factors USF1 and PDX-1 and protein kinase CK2 in pancreatic β-cells10.1038/s41598-017-16590-02045-2322https://doaj.org/article/2ec05ada4cd64bb4ab2b9b3d3a635f8d2017-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-16590-0https://doaj.org/toc/2045-2322Abstract Glucose homeostasis is regulated by insulin, which is produced in the β-cells of the pancreas. The synthesis of insulin is controlled by several transcription factors including PDX-1, USF1 and USF2. Both, PDX-1 and USF1 were identified as substrates for protein kinase CK2. Here, we have analysed the interplay of PDX-1, USF1 and CK2 in the regulation of PDX-1 gene transcription. We found that the PDX-1 promoter is dose-dependently transactivated by PDX-1 and transrepressed by USF1. With increasing glucose concentrations the transrepression of the PDX-1 promoter by USF1 is successively abrogated. PDX-1 binding to its own promoter was not influenced by glucose, whereas USF1 binding to the PDX-1 promoter was reduced. The same effect was observed after inhibition of the protein kinase activity by three different inhibitors or by using a phospho-mutant of USF1. Moreover, phosphorylation of USF1 by CK2 seems to strengthen the interaction between USF1 and PDX-1. Thus, CK2 is a negative regulator of the USF1-dependent PDX-1 transcription. Moreover, upon inhibition of CK2 in primary islets, insulin expression as well as insulin secretion were enhanced without affecting the viability of the cells. Therefore, inhibition of CK2 activity may be a promising approach to stimulate insulin production in pancreatic β-cells.Sarah SpohrerRebecca GroßLisa NalbachLisa SchwindHeike StumpfMichael D. MengerEmmanuel AmpofoMathias MontenarhClaudia GötzNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-17 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sarah Spohrer Rebecca Groß Lisa Nalbach Lisa Schwind Heike Stumpf Michael D. Menger Emmanuel Ampofo Mathias Montenarh Claudia Götz Functional interplay between the transcription factors USF1 and PDX-1 and protein kinase CK2 in pancreatic β-cells
description	Abstract Glucose homeostasis is regulated by insulin, which is produced in the β-cells of the pancreas. The synthesis of insulin is controlled by several transcription factors including PDX-1, USF1 and USF2. Both, PDX-1 and USF1 were identified as substrates for protein kinase CK2. Here, we have analysed the interplay of PDX-1, USF1 and CK2 in the regulation of PDX-1 gene transcription. We found that the PDX-1 promoter is dose-dependently transactivated by PDX-1 and transrepressed by USF1. With increasing glucose concentrations the transrepression of the PDX-1 promoter by USF1 is successively abrogated. PDX-1 binding to its own promoter was not influenced by glucose, whereas USF1 binding to the PDX-1 promoter was reduced. The same effect was observed after inhibition of the protein kinase activity by three different inhibitors or by using a phospho-mutant of USF1. Moreover, phosphorylation of USF1 by CK2 seems to strengthen the interaction between USF1 and PDX-1. Thus, CK2 is a negative regulator of the USF1-dependent PDX-1 transcription. Moreover, upon inhibition of CK2 in primary islets, insulin expression as well as insulin secretion were enhanced without affecting the viability of the cells. Therefore, inhibition of CK2 activity may be a promising approach to stimulate insulin production in pancreatic β-cells.
format	article
author	Sarah Spohrer Rebecca Groß Lisa Nalbach Lisa Schwind Heike Stumpf Michael D. Menger Emmanuel Ampofo Mathias Montenarh Claudia Götz
author_facet	Sarah Spohrer Rebecca Groß Lisa Nalbach Lisa Schwind Heike Stumpf Michael D. Menger Emmanuel Ampofo Mathias Montenarh Claudia Götz
author_sort	Sarah Spohrer
title	Functional interplay between the transcription factors USF1 and PDX-1 and protein kinase CK2 in pancreatic β-cells
title_short	Functional interplay between the transcription factors USF1 and PDX-1 and protein kinase CK2 in pancreatic β-cells
title_full	Functional interplay between the transcription factors USF1 and PDX-1 and protein kinase CK2 in pancreatic β-cells
title_fullStr	Functional interplay between the transcription factors USF1 and PDX-1 and protein kinase CK2 in pancreatic β-cells
title_full_unstemmed	Functional interplay between the transcription factors USF1 and PDX-1 and protein kinase CK2 in pancreatic β-cells
title_sort	functional interplay between the transcription factors usf1 and pdx-1 and protein kinase ck2 in pancreatic β-cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2ec05ada4cd64bb4ab2b9b3d3a635f8d
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Functional interplay between the transcription factors USF1 and PDX-1 and protein kinase CK2 in pancreatic β-cells

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