Differential impact of tetratricopeptide repeat proteins on the steroid hormone receptors.

<h4>Background</h4>Tetratricopeptide repeat (TPR) motif containing co-chaperones of the chaperone Hsp90 are considered control modules that govern activity and specificity of this central folding platform. Steroid receptors are paradigm clients of Hsp90. The influence of some TPR protein...

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Autores principales:	Jan-Philip Schülke, Gabriela Monika Wochnik, Isabelle Lang-Rollin, Nils Christian Gassen, Regina Theresia Knapp, Barbara Berning, Alexander Yassouridis, Theo Rein
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d7db7625a75d4d79b39d576bebe2efbe
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spelling	oai:doaj.org-article:d7db7625a75d4d79b39d576bebe2efbe2021-12-02T20:19:51ZDifferential impact of tetratricopeptide repeat proteins on the steroid hormone receptors.1932-620310.1371/journal.pone.0011717https://doaj.org/article/d7db7625a75d4d79b39d576bebe2efbe2010-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20661446/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Tetratricopeptide repeat (TPR) motif containing co-chaperones of the chaperone Hsp90 are considered control modules that govern activity and specificity of this central folding platform. Steroid receptors are paradigm clients of Hsp90. The influence of some TPR proteins on selected receptors has been described, but a comprehensive analysis of the effects of TPR proteins on all steroid receptors has not been accomplished yet.<h4>Methodology and principal findings</h4>We compared the influence of the TPR proteins FK506 binding proteins 51 and 52, protein phosphatase-5, C-terminus of Hsp70 interacting protein, cyclophillin 40, hepatitis-virus-B X-associated protein-2, and tetratricopeptide repeat protein-2 on all six steroid hormone receptors in a homogeneous mammalian cell system. To be able to assess each cofactor's effect on the transcriptional activity of on each steroid receptor we employed transient transfection in a reporter gene assay. In addition, we evaluated the interactions of the TPR proteins with the receptors and components of the Hsp90 chaperone heterocomplex by coimmunoprecipitation. In the functional assays, corticosteroid and progesterone receptors displayed the most sensitive and distinct reaction to the TPR proteins. Androgen receptor's activity was moderately impaired by most cofactors, whereas the Estrogen receptors' activity was impaired by most cofactors only to a minor degree. Second, interaction studies revealed that the strongly receptor-interacting co-chaperones were all among the inhibitory proteins. Intriguingly, the TPR-proteins also differentially co-precipitated the heterochaperone complex components Hsp90, Hsp70, and p23, pointing to differences in their modes of action.<h4>Conclusion and significance</h4>The results of this comprehensive study provide important insight into chaperoning of diverse client proteins via the combinatorial action of (co)-chaperones. The differential effects of the TPR proteins on steroid receptors bear on all physiological processes related to steroid hormone activity.Jan-Philip SchülkeGabriela Monika WochnikIsabelle Lang-RollinNils Christian GassenRegina Theresia KnappBarbara BerningAlexander YassouridisTheo ReinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 7, p e11717 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jan-Philip Schülke Gabriela Monika Wochnik Isabelle Lang-Rollin Nils Christian Gassen Regina Theresia Knapp Barbara Berning Alexander Yassouridis Theo Rein Differential impact of tetratricopeptide repeat proteins on the steroid hormone receptors.
description	<h4>Background</h4>Tetratricopeptide repeat (TPR) motif containing co-chaperones of the chaperone Hsp90 are considered control modules that govern activity and specificity of this central folding platform. Steroid receptors are paradigm clients of Hsp90. The influence of some TPR proteins on selected receptors has been described, but a comprehensive analysis of the effects of TPR proteins on all steroid receptors has not been accomplished yet.<h4>Methodology and principal findings</h4>We compared the influence of the TPR proteins FK506 binding proteins 51 and 52, protein phosphatase-5, C-terminus of Hsp70 interacting protein, cyclophillin 40, hepatitis-virus-B X-associated protein-2, and tetratricopeptide repeat protein-2 on all six steroid hormone receptors in a homogeneous mammalian cell system. To be able to assess each cofactor's effect on the transcriptional activity of on each steroid receptor we employed transient transfection in a reporter gene assay. In addition, we evaluated the interactions of the TPR proteins with the receptors and components of the Hsp90 chaperone heterocomplex by coimmunoprecipitation. In the functional assays, corticosteroid and progesterone receptors displayed the most sensitive and distinct reaction to the TPR proteins. Androgen receptor's activity was moderately impaired by most cofactors, whereas the Estrogen receptors' activity was impaired by most cofactors only to a minor degree. Second, interaction studies revealed that the strongly receptor-interacting co-chaperones were all among the inhibitory proteins. Intriguingly, the TPR-proteins also differentially co-precipitated the heterochaperone complex components Hsp90, Hsp70, and p23, pointing to differences in their modes of action.<h4>Conclusion and significance</h4>The results of this comprehensive study provide important insight into chaperoning of diverse client proteins via the combinatorial action of (co)-chaperones. The differential effects of the TPR proteins on steroid receptors bear on all physiological processes related to steroid hormone activity.
format	article
author	Jan-Philip Schülke Gabriela Monika Wochnik Isabelle Lang-Rollin Nils Christian Gassen Regina Theresia Knapp Barbara Berning Alexander Yassouridis Theo Rein
author_facet	Jan-Philip Schülke Gabriela Monika Wochnik Isabelle Lang-Rollin Nils Christian Gassen Regina Theresia Knapp Barbara Berning Alexander Yassouridis Theo Rein
author_sort	Jan-Philip Schülke
title	Differential impact of tetratricopeptide repeat proteins on the steroid hormone receptors.
title_short	Differential impact of tetratricopeptide repeat proteins on the steroid hormone receptors.
title_full	Differential impact of tetratricopeptide repeat proteins on the steroid hormone receptors.
title_fullStr	Differential impact of tetratricopeptide repeat proteins on the steroid hormone receptors.
title_full_unstemmed	Differential impact of tetratricopeptide repeat proteins on the steroid hormone receptors.
title_sort	differential impact of tetratricopeptide repeat proteins on the steroid hormone receptors.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/d7db7625a75d4d79b39d576bebe2efbe
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Differential impact of tetratricopeptide repeat proteins on the steroid hormone receptors.

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