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NF90–NF45 is essential for β cell compensation under obesity-inducing metabolic stress through suppression of p53 signaling pathway
The Nuclear Factor 90 (NF90)–NF45 complex has been known to regulate the progression of transcription, mRNA stability, translational inhibition, RNA export and microRNA biogenesis. However, the physiological functions of the NF90–NF45 complex remain unclear. We newly discovered that the NF90–NF45 co...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9132887/ https://www.ncbi.nlm.nih.gov/pubmed/35614067 http://dx.doi.org/10.1038/s41598-022-12600-y |
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author | Lai, Sylvia Higuchi, Takuma Tsuda, Masayuki Sugiyama, Yasunori Morisawa, Keiko Taniguchi, Taketoshi Sakamoto, Shuji |
author_facet | Lai, Sylvia Higuchi, Takuma Tsuda, Masayuki Sugiyama, Yasunori Morisawa, Keiko Taniguchi, Taketoshi Sakamoto, Shuji |
author_sort | Lai, Sylvia |
collection | PubMed |
description | The Nuclear Factor 90 (NF90)–NF45 complex has been known to regulate the progression of transcription, mRNA stability, translational inhibition, RNA export and microRNA biogenesis. However, the physiological functions of the NF90–NF45 complex remain unclear. We newly discovered that the NF90–NF45 complex was expressed in primary β cells and established cell lines. Therefore, in this study, we focused on the function of the endogenous NF90–NF45 complex in the β cells. To investigate this issue, we generated β-cell-specific NF90–NF45 deficient mice. These mice exhibited hyperglycaemia and lower plasma insulin levels under a high fat diet together with decreased islet mass. To uncover this mechanism, we performed a whole-genome expression microarray of the total RNA prepared from β cell lines treated with siRNAs targeting both NF90 and NF45. In this result, we found an activation of p53 signaling in the NF90–NF45-knockdown cells. This activation was supported by elevation of luciferase activity derived from a reporter plasmid harboring p53 binding sites in the NF90–NF45-knockdown cells. Furthermore, the knockdown of NF90–NF45 resulted in a significant retardation of the β cell line growth rates. Importantly, a dominant negative form of p53 rescues the growth retardation in BTC6 cells depleted of NF90–NF45, suggesting that NF90–NF45 would be positively involved in β cell proliferation through suppression of p53 signal pathway. Taken together, NF90–NF45 is essential for β cell compensation under obesity-inducing metabolic stress via repression of p53 signaling. |
format | Online Article Text |
id | pubmed-9132887 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-91328872022-05-27 NF90–NF45 is essential for β cell compensation under obesity-inducing metabolic stress through suppression of p53 signaling pathway Lai, Sylvia Higuchi, Takuma Tsuda, Masayuki Sugiyama, Yasunori Morisawa, Keiko Taniguchi, Taketoshi Sakamoto, Shuji Sci Rep Article The Nuclear Factor 90 (NF90)–NF45 complex has been known to regulate the progression of transcription, mRNA stability, translational inhibition, RNA export and microRNA biogenesis. However, the physiological functions of the NF90–NF45 complex remain unclear. We newly discovered that the NF90–NF45 complex was expressed in primary β cells and established cell lines. Therefore, in this study, we focused on the function of the endogenous NF90–NF45 complex in the β cells. To investigate this issue, we generated β-cell-specific NF90–NF45 deficient mice. These mice exhibited hyperglycaemia and lower plasma insulin levels under a high fat diet together with decreased islet mass. To uncover this mechanism, we performed a whole-genome expression microarray of the total RNA prepared from β cell lines treated with siRNAs targeting both NF90 and NF45. In this result, we found an activation of p53 signaling in the NF90–NF45-knockdown cells. This activation was supported by elevation of luciferase activity derived from a reporter plasmid harboring p53 binding sites in the NF90–NF45-knockdown cells. Furthermore, the knockdown of NF90–NF45 resulted in a significant retardation of the β cell line growth rates. Importantly, a dominant negative form of p53 rescues the growth retardation in BTC6 cells depleted of NF90–NF45, suggesting that NF90–NF45 would be positively involved in β cell proliferation through suppression of p53 signal pathway. Taken together, NF90–NF45 is essential for β cell compensation under obesity-inducing metabolic stress via repression of p53 signaling. Nature Publishing Group UK 2022-05-25 /pmc/articles/PMC9132887/ /pubmed/35614067 http://dx.doi.org/10.1038/s41598-022-12600-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Lai, Sylvia Higuchi, Takuma Tsuda, Masayuki Sugiyama, Yasunori Morisawa, Keiko Taniguchi, Taketoshi Sakamoto, Shuji NF90–NF45 is essential for β cell compensation under obesity-inducing metabolic stress through suppression of p53 signaling pathway |
title | NF90–NF45 is essential for β cell compensation under obesity-inducing metabolic stress through suppression of p53 signaling pathway |
title_full | NF90–NF45 is essential for β cell compensation under obesity-inducing metabolic stress through suppression of p53 signaling pathway |
title_fullStr | NF90–NF45 is essential for β cell compensation under obesity-inducing metabolic stress through suppression of p53 signaling pathway |
title_full_unstemmed | NF90–NF45 is essential for β cell compensation under obesity-inducing metabolic stress through suppression of p53 signaling pathway |
title_short | NF90–NF45 is essential for β cell compensation under obesity-inducing metabolic stress through suppression of p53 signaling pathway |
title_sort | nf90–nf45 is essential for β cell compensation under obesity-inducing metabolic stress through suppression of p53 signaling pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9132887/ https://www.ncbi.nlm.nih.gov/pubmed/35614067 http://dx.doi.org/10.1038/s41598-022-12600-y |
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