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FOXP3 Activates SUMO-Conjugating UBC9 Gene in MCF7 Breast Cancer Cells
Forkhead Box Protein P3 (FOXP3), a transcription factor of the FOX protein family, is essentially involved in the development of regulatory T (Treg) cells, and functions as a tumor suppressor. Although FOXP3 has been widely studied in immune system and cancer development, its function in the regulat...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073147/ https://www.ncbi.nlm.nih.gov/pubmed/30011797 http://dx.doi.org/10.3390/ijms19072036 |
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author | Wang, Chiung-Min Yang, William H. Liu, Runhua Wang, Lizhong Yang, Wei-Hsiung |
author_facet | Wang, Chiung-Min Yang, William H. Liu, Runhua Wang, Lizhong Yang, Wei-Hsiung |
author_sort | Wang, Chiung-Min |
collection | PubMed |
description | Forkhead Box Protein P3 (FOXP3), a transcription factor of the FOX protein family, is essentially involved in the development of regulatory T (Treg) cells, and functions as a tumor suppressor. Although FOXP3 has been widely studied in immune system and cancer development, its function in the regulation of the UBC9 gene (for the sole E2 enzyme of SUMOylation) is unknown. Herein, we find that the overexpression of FOXP3 in human MCF7 breast cancer cells increases the level of UBC9 mRNA. Moreover, the level of UBC9 protein dose-dependently increases in the FOXP3-Tet-off MCF7 cells. Notably, the promoter activity of the UBC9 is activated by FOXP3 in a dose-dependent manner in both the MCF7 and HEK293 cells. Next, by mapping the UBC9 promoter as well as the site-directed mutagenesis and ChIP analysis, we show that the FOXP3 response element at the −310 bp region, but not the −2182 bp region, is mainly required for UBC9 activation by FOXP3. Finally, we demonstrate that the removal of phosphorylation (S418A and Y342F) and the removal of acetylation/ubiquitination (K263R and K263RK268R) of the FOXP3 result in attenuated transcriptional activity of UBC9. Taken together, FOXP3 acts as a novel transcriptional activator of the human UBC9 gene, suggesting that FOXP3 may have physiological functions as a novel player in global SUMOylation, as well as other post-translational modification systems. |
format | Online Article Text |
id | pubmed-6073147 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-60731472018-08-13 FOXP3 Activates SUMO-Conjugating UBC9 Gene in MCF7 Breast Cancer Cells Wang, Chiung-Min Yang, William H. Liu, Runhua Wang, Lizhong Yang, Wei-Hsiung Int J Mol Sci Article Forkhead Box Protein P3 (FOXP3), a transcription factor of the FOX protein family, is essentially involved in the development of regulatory T (Treg) cells, and functions as a tumor suppressor. Although FOXP3 has been widely studied in immune system and cancer development, its function in the regulation of the UBC9 gene (for the sole E2 enzyme of SUMOylation) is unknown. Herein, we find that the overexpression of FOXP3 in human MCF7 breast cancer cells increases the level of UBC9 mRNA. Moreover, the level of UBC9 protein dose-dependently increases in the FOXP3-Tet-off MCF7 cells. Notably, the promoter activity of the UBC9 is activated by FOXP3 in a dose-dependent manner in both the MCF7 and HEK293 cells. Next, by mapping the UBC9 promoter as well as the site-directed mutagenesis and ChIP analysis, we show that the FOXP3 response element at the −310 bp region, but not the −2182 bp region, is mainly required for UBC9 activation by FOXP3. Finally, we demonstrate that the removal of phosphorylation (S418A and Y342F) and the removal of acetylation/ubiquitination (K263R and K263RK268R) of the FOXP3 result in attenuated transcriptional activity of UBC9. Taken together, FOXP3 acts as a novel transcriptional activator of the human UBC9 gene, suggesting that FOXP3 may have physiological functions as a novel player in global SUMOylation, as well as other post-translational modification systems. MDPI 2018-07-13 /pmc/articles/PMC6073147/ /pubmed/30011797 http://dx.doi.org/10.3390/ijms19072036 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wang, Chiung-Min Yang, William H. Liu, Runhua Wang, Lizhong Yang, Wei-Hsiung FOXP3 Activates SUMO-Conjugating UBC9 Gene in MCF7 Breast Cancer Cells |
title | FOXP3 Activates SUMO-Conjugating UBC9 Gene in MCF7 Breast Cancer Cells |
title_full | FOXP3 Activates SUMO-Conjugating UBC9 Gene in MCF7 Breast Cancer Cells |
title_fullStr | FOXP3 Activates SUMO-Conjugating UBC9 Gene in MCF7 Breast Cancer Cells |
title_full_unstemmed | FOXP3 Activates SUMO-Conjugating UBC9 Gene in MCF7 Breast Cancer Cells |
title_short | FOXP3 Activates SUMO-Conjugating UBC9 Gene in MCF7 Breast Cancer Cells |
title_sort | foxp3 activates sumo-conjugating ubc9 gene in mcf7 breast cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073147/ https://www.ncbi.nlm.nih.gov/pubmed/30011797 http://dx.doi.org/10.3390/ijms19072036 |
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