NF-κB transcriptional activity is modulated by FK506-Binding proteins FKBP51 and FKBP52:A role for peptidyl-prolyl isomerase activity

Hsp90 binding immunophilins FKBP51 and FKBP52 modulate steroid receptor trafficking and hormone-dependent biological responses. With the purpose to expand this model to other nuclear factors that are also subject to nuclear-cytoplasmic shuttling, we analyzed whether these immunophilins modulate NF-κ...

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Autor principal:	Fontana, Vanina Andrea
Publicado:	2014
Materias:	fk 506 binding protein glucocorticoid receptor protein binding RELA protein, human tacrolimus binding protein 4 tacrolimus binding protein 5 transcription factor RelA active transport animal cell nucleus genetic transcription HEK293 cell line human metabolism physiology promoter region protein domain rat transcription initiation Active Transport, Cell Nucleus Animals Cell Nucleus HEK293 Cells Humans Promoter Regions, Genetic Protein Binding Protein Interaction Domains and Motifs Rats Receptors, Glucocorticoid Tacrolimus Binding Proteins Transcription Factor RelA Transcription, Genetic Transcriptional Activation
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v289_n38_p26263_Erlejman http://hdl.handle.net/20.500.12110/paper_00219258_v289_n38_p26263_Erlejman
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_00219258_v289_n38_p26263_Erlejman
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spelling	paper:paper_00219258_v289_n38_p26263_Erlejman2025-07-30T17:25:57Z NF-κB transcriptional activity is modulated by FK506-Binding proteins FKBP51 and FKBP52:A role for peptidyl-prolyl isomerase activity Fontana, Vanina Andrea fk 506 binding protein glucocorticoid receptor protein binding RELA protein, human tacrolimus binding protein 4 tacrolimus binding protein 5 transcription factor RelA active transport animal cell nucleus genetic transcription HEK293 cell line human metabolism physiology promoter region protein domain rat transcription initiation Active Transport, Cell Nucleus Animals Cell Nucleus HEK293 Cells Humans Promoter Regions, Genetic Protein Binding Protein Interaction Domains and Motifs Rats Receptors, Glucocorticoid Tacrolimus Binding Proteins Transcription Factor RelA Transcription, Genetic Transcriptional Activation Hsp90 binding immunophilins FKBP51 and FKBP52 modulate steroid receptor trafficking and hormone-dependent biological responses. With the purpose to expand this model to other nuclear factors that are also subject to nuclear-cytoplasmic shuttling, we analyzed whether these immunophilins modulate NF-κB signaling. It is demonstrated that FKBP51 impairs both the nuclear translocation rate of NF-κB and its transcriptional activity. The inhibitory action of FKBP51 requires neither the peptidylprolyl-isomerase activity of the immunophilin nor its association with Hsp90. The TPR domain of FKBP51 is essential. On the other hand, FKBP52 favors the nuclear retention time of RelA, its association to a DNA consensus binding sequence, and NF-κB transcriptional activity, the latter effect being strongly dependent on the peptidylprolyl-isomerase activity and also on the TPR domain of FKBP52, but its interaction with Hsp90 is not required. In unstimulated cells, FKBP51 forms endogenous complexes with cytoplasmic RelA. Upon cell stimulation with phorbol ester, the NF-κB soluble complex exchanges FKBP51 for FKBP52, and the NF-κB biological effect is triggered. Importantly, FKBP52 is functionally recruited to the promoter region of NF-κB target genes, whereas FKBP51 is released. Competition assays demonstrated that both immunophilins antagonize one another, and binding assays with purified proteins suggest that the association of RelA and immunophilins could be direct. These observations suggest that the biological action of NF-κB in different cell types could be positively regulated by a high FKBP52/FKBP51 expression ratio by favoring NF-κB nuclear retention, recruitment to the promoter regions of target genes, and transcriptional activity Fil:Fontana, V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2014 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v289_n38_p26263_Erlejman http://hdl.handle.net/20.500.12110/paper_00219258_v289_n38_p26263_Erlejman
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	fk 506 binding protein glucocorticoid receptor protein binding RELA protein, human tacrolimus binding protein 4 tacrolimus binding protein 5 transcription factor RelA active transport animal cell nucleus genetic transcription HEK293 cell line human metabolism physiology promoter region protein domain rat transcription initiation Active Transport, Cell Nucleus Animals Cell Nucleus HEK293 Cells Humans Promoter Regions, Genetic Protein Binding Protein Interaction Domains and Motifs Rats Receptors, Glucocorticoid Tacrolimus Binding Proteins Transcription Factor RelA Transcription, Genetic Transcriptional Activation
spellingShingle	fk 506 binding protein glucocorticoid receptor protein binding RELA protein, human tacrolimus binding protein 4 tacrolimus binding protein 5 transcription factor RelA active transport animal cell nucleus genetic transcription HEK293 cell line human metabolism physiology promoter region protein domain rat transcription initiation Active Transport, Cell Nucleus Animals Cell Nucleus HEK293 Cells Humans Promoter Regions, Genetic Protein Binding Protein Interaction Domains and Motifs Rats Receptors, Glucocorticoid Tacrolimus Binding Proteins Transcription Factor RelA Transcription, Genetic Transcriptional Activation Fontana, Vanina Andrea NF-κB transcriptional activity is modulated by FK506-Binding proteins FKBP51 and FKBP52:A role for peptidyl-prolyl isomerase activity
topic_facet	fk 506 binding protein glucocorticoid receptor protein binding RELA protein, human tacrolimus binding protein 4 tacrolimus binding protein 5 transcription factor RelA active transport animal cell nucleus genetic transcription HEK293 cell line human metabolism physiology promoter region protein domain rat transcription initiation Active Transport, Cell Nucleus Animals Cell Nucleus HEK293 Cells Humans Promoter Regions, Genetic Protein Binding Protein Interaction Domains and Motifs Rats Receptors, Glucocorticoid Tacrolimus Binding Proteins Transcription Factor RelA Transcription, Genetic Transcriptional Activation
description	Hsp90 binding immunophilins FKBP51 and FKBP52 modulate steroid receptor trafficking and hormone-dependent biological responses. With the purpose to expand this model to other nuclear factors that are also subject to nuclear-cytoplasmic shuttling, we analyzed whether these immunophilins modulate NF-κB signaling. It is demonstrated that FKBP51 impairs both the nuclear translocation rate of NF-κB and its transcriptional activity. The inhibitory action of FKBP51 requires neither the peptidylprolyl-isomerase activity of the immunophilin nor its association with Hsp90. The TPR domain of FKBP51 is essential. On the other hand, FKBP52 favors the nuclear retention time of RelA, its association to a DNA consensus binding sequence, and NF-κB transcriptional activity, the latter effect being strongly dependent on the peptidylprolyl-isomerase activity and also on the TPR domain of FKBP52, but its interaction with Hsp90 is not required. In unstimulated cells, FKBP51 forms endogenous complexes with cytoplasmic RelA. Upon cell stimulation with phorbol ester, the NF-κB soluble complex exchanges FKBP51 for FKBP52, and the NF-κB biological effect is triggered. Importantly, FKBP52 is functionally recruited to the promoter region of NF-κB target genes, whereas FKBP51 is released. Competition assays demonstrated that both immunophilins antagonize one another, and binding assays with purified proteins suggest that the association of RelA and immunophilins could be direct. These observations suggest that the biological action of NF-κB in different cell types could be positively regulated by a high FKBP52/FKBP51 expression ratio by favoring NF-κB nuclear retention, recruitment to the promoter regions of target genes, and transcriptional activity
author	Fontana, Vanina Andrea
author_facet	Fontana, Vanina Andrea
author_sort	Fontana, Vanina Andrea
title	NF-κB transcriptional activity is modulated by FK506-Binding proteins FKBP51 and FKBP52:A role for peptidyl-prolyl isomerase activity
title_short	NF-κB transcriptional activity is modulated by FK506-Binding proteins FKBP51 and FKBP52:A role for peptidyl-prolyl isomerase activity
title_full	NF-κB transcriptional activity is modulated by FK506-Binding proteins FKBP51 and FKBP52:A role for peptidyl-prolyl isomerase activity
title_fullStr	NF-κB transcriptional activity is modulated by FK506-Binding proteins FKBP51 and FKBP52:A role for peptidyl-prolyl isomerase activity
title_full_unstemmed	NF-κB transcriptional activity is modulated by FK506-Binding proteins FKBP51 and FKBP52:A role for peptidyl-prolyl isomerase activity
title_sort	nf-κb transcriptional activity is modulated by fk506-binding proteins fkbp51 and fkbp52:a role for peptidyl-prolyl isomerase activity
publishDate	2014
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v289_n38_p26263_Erlejman http://hdl.handle.net/20.500.12110/paper_00219258_v289_n38_p26263_Erlejman
work_keys_str_mv	AT fontanavaninaandrea nfkbtranscriptionalactivityismodulatedbyfk506bindingproteinsfkbp51andfkbp52aroleforpeptidylprolylisomeraseactivity
_version_	1840323318802022400

NF-κB transcriptional activity is modulated by FK506-Binding proteins FKBP51 and FKBP52:A role for peptidyl-prolyl isomerase activity

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