Cargando…
Forkhead Box Protein P3 (FOXP3) Represses ATF3 Transcriptional Activity
Activating transcription factor 3 (ATF3), a transcription factor and acute stress sensor, is rapidly induced by a variety of pathophysiological signals and is essential in the complex processes in cellular stress response. FOXP3, a well-known breast and prostate tumor suppressor from the X chromosom...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583784/ https://www.ncbi.nlm.nih.gov/pubmed/34768829 http://dx.doi.org/10.3390/ijms222111400 |
_version_ | 1784597286990381056 |
---|---|
author | Wang, Chiung-Min Yang, William Harry Cardoso, Leticia Gutierrez, Ninoska Yang, Richard Henry Yang, Wei-Hsiung |
author_facet | Wang, Chiung-Min Yang, William Harry Cardoso, Leticia Gutierrez, Ninoska Yang, Richard Henry Yang, Wei-Hsiung |
author_sort | Wang, Chiung-Min |
collection | PubMed |
description | Activating transcription factor 3 (ATF3), a transcription factor and acute stress sensor, is rapidly induced by a variety of pathophysiological signals and is essential in the complex processes in cellular stress response. FOXP3, a well-known breast and prostate tumor suppressor from the X chromosome, is a novel transcriptional repressor for several oncogenes. However, it remains unknown whether ATF3 is the target protein of FOXP3. Herein, we demonstrate that ATF3 expression is regulated by FOXP3. Firstly, we observed that overexpression of FOXP3 reduced ATF3 protein level. Moreover, knockdown FOXP3 by siRNA increased ATF3 expression. Secondly, FOXP3 dose-dependently reduced ATF3 promoter activity in the luciferase reporter assay. Since FOXP3 is regulated by post-translational modifications (PTMs), we next investigated whether PTMs affect FOXP3-mediated ATF3 expression. Interestingly, we observed that phosphorylation mutation on FOXP3 (Y342F) significantly abolished FOXP3-mediated ATF3 expression. However, other PTM mutations on FOXP3, including S418 phosphorylation, K263 acetylation and ubiquitination, and K268 acetylation and ubiquitination, did not alter FOXP3-mediated ATF3 expression. Finally, the FOXP3 binding site was found on ATF3 promoter region by deletion and mutagenesis analysis. Taken together, our results suggest that FOXP3 functions as a novel regulator of ATF3 and that this novel event may be involved in tumor development and progression. |
format | Online Article Text |
id | pubmed-8583784 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85837842021-11-12 Forkhead Box Protein P3 (FOXP3) Represses ATF3 Transcriptional Activity Wang, Chiung-Min Yang, William Harry Cardoso, Leticia Gutierrez, Ninoska Yang, Richard Henry Yang, Wei-Hsiung Int J Mol Sci Article Activating transcription factor 3 (ATF3), a transcription factor and acute stress sensor, is rapidly induced by a variety of pathophysiological signals and is essential in the complex processes in cellular stress response. FOXP3, a well-known breast and prostate tumor suppressor from the X chromosome, is a novel transcriptional repressor for several oncogenes. However, it remains unknown whether ATF3 is the target protein of FOXP3. Herein, we demonstrate that ATF3 expression is regulated by FOXP3. Firstly, we observed that overexpression of FOXP3 reduced ATF3 protein level. Moreover, knockdown FOXP3 by siRNA increased ATF3 expression. Secondly, FOXP3 dose-dependently reduced ATF3 promoter activity in the luciferase reporter assay. Since FOXP3 is regulated by post-translational modifications (PTMs), we next investigated whether PTMs affect FOXP3-mediated ATF3 expression. Interestingly, we observed that phosphorylation mutation on FOXP3 (Y342F) significantly abolished FOXP3-mediated ATF3 expression. However, other PTM mutations on FOXP3, including S418 phosphorylation, K263 acetylation and ubiquitination, and K268 acetylation and ubiquitination, did not alter FOXP3-mediated ATF3 expression. Finally, the FOXP3 binding site was found on ATF3 promoter region by deletion and mutagenesis analysis. Taken together, our results suggest that FOXP3 functions as a novel regulator of ATF3 and that this novel event may be involved in tumor development and progression. MDPI 2021-10-22 /pmc/articles/PMC8583784/ /pubmed/34768829 http://dx.doi.org/10.3390/ijms222111400 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wang, Chiung-Min Yang, William Harry Cardoso, Leticia Gutierrez, Ninoska Yang, Richard Henry Yang, Wei-Hsiung Forkhead Box Protein P3 (FOXP3) Represses ATF3 Transcriptional Activity |
title | Forkhead Box Protein P3 (FOXP3) Represses ATF3 Transcriptional Activity |
title_full | Forkhead Box Protein P3 (FOXP3) Represses ATF3 Transcriptional Activity |
title_fullStr | Forkhead Box Protein P3 (FOXP3) Represses ATF3 Transcriptional Activity |
title_full_unstemmed | Forkhead Box Protein P3 (FOXP3) Represses ATF3 Transcriptional Activity |
title_short | Forkhead Box Protein P3 (FOXP3) Represses ATF3 Transcriptional Activity |
title_sort | forkhead box protein p3 (foxp3) represses atf3 transcriptional activity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583784/ https://www.ncbi.nlm.nih.gov/pubmed/34768829 http://dx.doi.org/10.3390/ijms222111400 |
work_keys_str_mv | AT wangchiungmin forkheadboxproteinp3foxp3repressesatf3transcriptionalactivity AT yangwilliamharry forkheadboxproteinp3foxp3repressesatf3transcriptionalactivity AT cardosoleticia forkheadboxproteinp3foxp3repressesatf3transcriptionalactivity AT gutierrezninoska forkheadboxproteinp3foxp3repressesatf3transcriptionalactivity AT yangrichardhenry forkheadboxproteinp3foxp3repressesatf3transcriptionalactivity AT yangweihsiung forkheadboxproteinp3foxp3repressesatf3transcriptionalactivity |