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...

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Autores principales:	Chiung-Min Wang, William Harry Yang, Leticia Cardoso, Ninoska Gutierrez, Richard Henry Yang, Wei-Hsiung Yang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	FOXP3 ATF3 post-translational modification transcriptional activity Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/d32722bc37014aef959d79acfd9ee1ed
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spelling	oai:doaj.org-article:d32722bc37014aef959d79acfd9ee1ed2021-11-11T16:52:29ZForkhead Box Protein P3 (FOXP3) Represses ATF3 Transcriptional Activity10.3390/ijms2221114001422-00671661-6596https://doaj.org/article/d32722bc37014aef959d79acfd9ee1ed2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11400https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Activating 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.Chiung-Min WangWilliam Harry YangLeticia CardosoNinoska GutierrezRichard Henry YangWei-Hsiung YangMDPI AGarticleFOXP3ATF3post-translational modificationtranscriptional activityBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11400, p 11400 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	FOXP3 ATF3 post-translational modification transcriptional activity Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	FOXP3 ATF3 post-translational modification transcriptional activity Biology (General) QH301-705.5 Chemistry QD1-999 Chiung-Min Wang William Harry Yang Leticia Cardoso Ninoska Gutierrez Richard Henry Yang Wei-Hsiung Yang Forkhead Box Protein P3 (FOXP3) Represses ATF3 Transcriptional Activity
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	article
author	Chiung-Min Wang William Harry Yang Leticia Cardoso Ninoska Gutierrez Richard Henry Yang Wei-Hsiung Yang
author_facet	Chiung-Min Wang William Harry Yang Leticia Cardoso Ninoska Gutierrez Richard Henry Yang Wei-Hsiung Yang
author_sort	Chiung-Min Wang
title	Forkhead Box Protein P3 (FOXP3) Represses ATF3 Transcriptional Activity
title_short	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_sort	forkhead box protein p3 (foxp3) represses atf3 transcriptional activity
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d32722bc37014aef959d79acfd9ee1ed
work_keys_str_mv	AT chiungminwang forkheadboxproteinp3foxp3repressesatf3transcriptionalactivity AT williamharryyang forkheadboxproteinp3foxp3repressesatf3transcriptionalactivity AT leticiacardoso forkheadboxproteinp3foxp3repressesatf3transcriptionalactivity AT ninoskagutierrez forkheadboxproteinp3foxp3repressesatf3transcriptionalactivity AT richardhenryyang forkheadboxproteinp3foxp3repressesatf3transcriptionalactivity AT weihsiungyang forkheadboxproteinp3foxp3repressesatf3transcriptionalactivity
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Forkhead Box Protein P3 (FOXP3) Represses ATF3 Transcriptional Activity

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