Forkhead transcription factor FOXP3 upregulates CD25 expression through cooperation with RelA/NF-κB.

Considerable evidence supports the prediction that CD25 is directly regulated by the forkhead transcription factor FOXP3. However, given that CD25 is normally upregulated in activated T cells, regardless of whether they express FOXP3, this issue has still to be definitively demonstrated. Here we des...

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Autores principales: Cristina Camperio, Silvana Caristi, Giorgia Fanelli, Marzia Soligo, Paola Del Porto, Enza Piccolella
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Publicado: Public Library of Science (PLoS) 2012
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Acceso en línea:https://doaj.org/article/cce13a57d32443578a4e6bbe4542237f
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spelling oai:doaj.org-article:cce13a57d32443578a4e6bbe4542237f2021-11-18T08:10:44ZForkhead transcription factor FOXP3 upregulates CD25 expression through cooperation with RelA/NF-κB.1932-620310.1371/journal.pone.0048303https://doaj.org/article/cce13a57d32443578a4e6bbe4542237f2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23144749/?tool=EBIhttps://doaj.org/toc/1932-6203Considerable evidence supports the prediction that CD25 is directly regulated by the forkhead transcription factor FOXP3. However, given that CD25 is normally upregulated in activated T cells, regardless of whether they express FOXP3, this issue has still to be definitively demonstrated. Here we describe that FOXP3, induced by CD28 signals in human CD4(+)CD25(-) T lymphocytes, synergizes with RelA on a regulatory region of Cd25 promoter to mediate the transcriptional activation of Cd25 gene. We found that a striking feature of this regulatory region is the presence of a κB site and of two tandem copies of a non-consensus FOXP3 binding site separated at 5' ends by 19 nucleotides that allow FOXP3 and RelA binding to DNA and their physical interaction. The occupancy of the two FOXP3 binding sites in conjunction with RelA binding site occupancy allows FOXP3 to function as a positive activator of Cd25 gene. Indeed mutations of both FOXP3 binding sites such as mutation of κB site on Cd25 promoter abolished FOXP3 activatory functions. Moreover, FOXP3 mutation ΔE251, that compromises FOXP3 homotypic interactions, failed to trans activate Cd25 promoter, suggesting that both FOXP3 DNA binding and dimerization are required to trans activate Cd25 promoter. These findings identify a novel mechanism by which RelA and FOXP3 cooperate to mediate transcriptional regulation of target genes and characterize a region on Cd25 promoter where FOXP3 dimer could bridge intramolecularly two DNA sites and trans activate Cd25 gene.Cristina CamperioSilvana CaristiGiorgia FanelliMarzia SoligoPaola Del PortoEnza PiccolellaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e48303 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Cristina Camperio
Silvana Caristi
Giorgia Fanelli
Marzia Soligo
Paola Del Porto
Enza Piccolella
Forkhead transcription factor FOXP3 upregulates CD25 expression through cooperation with RelA/NF-κB.
description Considerable evidence supports the prediction that CD25 is directly regulated by the forkhead transcription factor FOXP3. However, given that CD25 is normally upregulated in activated T cells, regardless of whether they express FOXP3, this issue has still to be definitively demonstrated. Here we describe that FOXP3, induced by CD28 signals in human CD4(+)CD25(-) T lymphocytes, synergizes with RelA on a regulatory region of Cd25 promoter to mediate the transcriptional activation of Cd25 gene. We found that a striking feature of this regulatory region is the presence of a κB site and of two tandem copies of a non-consensus FOXP3 binding site separated at 5' ends by 19 nucleotides that allow FOXP3 and RelA binding to DNA and their physical interaction. The occupancy of the two FOXP3 binding sites in conjunction with RelA binding site occupancy allows FOXP3 to function as a positive activator of Cd25 gene. Indeed mutations of both FOXP3 binding sites such as mutation of κB site on Cd25 promoter abolished FOXP3 activatory functions. Moreover, FOXP3 mutation ΔE251, that compromises FOXP3 homotypic interactions, failed to trans activate Cd25 promoter, suggesting that both FOXP3 DNA binding and dimerization are required to trans activate Cd25 promoter. These findings identify a novel mechanism by which RelA and FOXP3 cooperate to mediate transcriptional regulation of target genes and characterize a region on Cd25 promoter where FOXP3 dimer could bridge intramolecularly two DNA sites and trans activate Cd25 gene.
format article
author Cristina Camperio
Silvana Caristi
Giorgia Fanelli
Marzia Soligo
Paola Del Porto
Enza Piccolella
author_facet Cristina Camperio
Silvana Caristi
Giorgia Fanelli
Marzia Soligo
Paola Del Porto
Enza Piccolella
author_sort Cristina Camperio
title Forkhead transcription factor FOXP3 upregulates CD25 expression through cooperation with RelA/NF-κB.
title_short Forkhead transcription factor FOXP3 upregulates CD25 expression through cooperation with RelA/NF-κB.
title_full Forkhead transcription factor FOXP3 upregulates CD25 expression through cooperation with RelA/NF-κB.
title_fullStr Forkhead transcription factor FOXP3 upregulates CD25 expression through cooperation with RelA/NF-κB.
title_full_unstemmed Forkhead transcription factor FOXP3 upregulates CD25 expression through cooperation with RelA/NF-κB.
title_sort forkhead transcription factor foxp3 upregulates cd25 expression through cooperation with rela/nf-κb.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/cce13a57d32443578a4e6bbe4542237f
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