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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...

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Autores principales: Wang, Chiung-Min, Yang, William H., Liu, Runhua, Wang, Lizhong, Yang, Wei-Hsiung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
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.
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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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